Immune landscape and response to oncolytic virus-based immunotherapy

Abstract

Oncolytic virus (OV)-based immunotherapy has emerged as a promising strategy for cancer treatment, offering a unique potential to selectively target malignant cells while sparing normal tissues. However, the immunosuppressive nature of tumor microenvironment (TME) poses a substantial hurdle to the development of OVs as effective immunotherapeutic agents, as it restricts the activation and recruitment of immune cells. This review elucidates the potential of OV-based immunotherapy in modulating the immune landscape within the TME to overcome immune resistance and enhance antitumor immune responses. We examine the role of OVs in targeting specific immune cell populations, including dendritic cells, T cells, natural killer cells, and macrophages, and their ability to alter the TME by inhibiting angiogenesis and reducing tumor fibrosis. Additionally, we explore strategies to optimize OV-based drug delivery and improve the efficiency of OV-mediated immunotherapy. In conclusion, this review offers a concise and comprehensive synopsis of the current status and future prospects of OV-based immunotherapy, underscoring its remarkable potential as an effective immunotherapeutic agent for cancer treatment.

Keywords

oncolytic virus / immunotherapy / immunotherapeutic agents / immune landscape

References

[1] Ferrucci PF, Pala L, Conforti F, Cocorocchio E. Talimogene laherparepvec (T-VEC): an intralesional cancer immunotherapy for advanced melanoma. Cancers (Basel) 2021; 13(6): 1383

[2] Todo T, Ito H, Ino Y, Ohtsu H, Ota Y, Shibahara J, Tanaka M. Intratumoral oncolytic herpes virus G47∆ for residual or recurrent glioblastoma: a phase 2 trial. Nat Med 2022; 28(8): 1630–1639

[3] Qiao Q, Song M, Song C, Zhang Y, Wang X, Huang Q, Wang B, Yang P, Zhao S, Li Y, Wang Z, Zhao J. Single-dose vaccination of recombinant chimeric newcastle disease virus (NDV) LaSota vaccine strain expressing infectious bursal disease virus (IBDV) VP2 gene provides full protection against genotype VII NDV and IBDV challenge. Vaccines (Basel) 2021; 9(12): 1483

[4] Vijayakumar G, Palese P, Goff PH. Oncolytic Newcastle disease virus expressing a checkpoint inhibitor as a radioenhancing agent for murine melanoma. EBioMedicine 2019; 49: 96–105

[5] Huang Z, Liu M, Huang Y. Oncolytic therapy and gene therapy for cancer: recent advances in antitumor effects of Newcastle disease virus. Discov Med 2020; 30(159): 39–48

[6] Keshavarz M, Nejad ASM, Esghaei M, Bokharaei-Salim F, Dianat-Moghadam H, Keyvani H, Ghaemi A. Oncolytic Newcastle disease virus reduces growth of cervical cancer cell by inducing apoptosis. Saudi J Biol Sci 2020; 27(1): 47–52

[7] Jiffry J, Thavornwatanayong T, Rao D, Fogel EJ, Saytoo D, Nahata R, Guzik H, Chaudhary I, Augustine T, Goel S, Maitra R. Oncolytic reovirus (pelareorep) induces autophagy in KRAS-mutated colorectal cancer. Clin Cancer Res 2021; 27(3): 865–876

[8] Kennedy BE, Murphy JP, Clements DR, Konda P, Holay N, Kim Y, Pathak GP, Giacomantonio MA, Hiani YE, Gujar S. Inhibition of pyruvate dehydrogenase kinase enhances the antitumor efficacy of oncolytic reovirus. Cancer Res 2019; 79(15): 3824–3836

[9] Gebremeskel S, Nelson A, Walker B, Oliphant T, Lobert L, Mahoney D, Johnston B. Natural killer T cell immunotherapy combined with oncolytic vesicular stomatitis virus or reovirus treatments differentially increases survival in mouse models of ovarian and breast cancer metastasis. J Immunother Cancer 2021; 9(3): e002096

[10] Abudoureyimu M, Lai Y, Tian C, Wang T, Wang R, Chu X. Oncolytic adenovirus—a Nova for gene-targeted oncolytic viral therapy in HCC. Front Oncol 2019; 9: 1182

[11] Mahasa KJ, de Pillis L, Ouifki R, Eladdadi A, Maini P, Yoon AR, Yun CO. Mesenchymal stem cells used as carrier cells of oncolytic adenovirus results in enhanced oncolytic virotherapy. Sci Rep 2020; 10(1): 425

[12] Sato-Dahlman M, LaRocca CJ, Yanagiba C, Yamamoto M. Adenovirus and immunotherapy: advancing cancer treatment by combination. Cancers (Basel) 2020; 12(5): 1295

[13] Matsunaga W, Gotoh A. Adenovirus as a vector and oncolytic virus. Curr Issues Mol Biol 2023; 45(6): 4826–4840

[14] Zhao Y, Liu Z, Li L, Wu J, Zhang H, Zhang H, Lei T, Xu B. Oncolytic adenovirus: prospects for cancer immunotherapy. Front Microbiol 2021; 12: 707290

[15] Blanchette P, Teodoro JG. A renaissance for oncolytic adenoviruses?. Viruses 2023; 15(2): 358

[16] Cook J, Peng KW, Witzig TE, Broski SM, Villasboas JC, Paludo J, Patnaik M, Rajkumar V, Dispenzieri A, Leung N, Buadi F, Bennani N, Ansell SM, Zhang L, Packiriswamy N, Balakrishnan B, Brunton B, Giers M, Ginos B, Dueck AC, Geyer S, Gertz MA, Warsame R, Go RS, Hayman SR, Dingli D, Kumar S, Bergsagel L, Munoz JL, Gonsalves W, Kourelis T, Muchtar E, Kapoor P, Kyle RA, Lin Y, Siddiqui M, Fonder A, Hobbs M, Hwa L, Naik S, Russell SJ, Lacy MQ. Clinical activity of single-dose systemic oncolytic VSV virotherapy in patients with relapsed refractory T-cell lymphoma. Blood Adv 2022; 6(11): 3268–3279

[17] Hastie E, Grdzelishvili VZ. Vesicular stomatitis virus as a flexible platform for oncolytic virotherapy against cancer. J Gen Virol 2012; 93(Pt 12): 2529–2545

[18] Felt SA, Grdzelishvili VZ. Recent advances in vesicular stomatitis virus-based oncolytic virotherapy: a 5-year update. J Gen Virol 2017; 98(12): 2895–2911

[19] Barber GN. Vesicular stomatitis virus as an oncolytic vector. Viral Immunol 2004; 17(4): 516–527

[20] Diaz RM, Galivo F, Kottke T, Wongthida P, Qiao J, Thompson J, Valdes M, Barber G, Vile RG. Oncolytic immunovirotherapy for melanoma using vesicular stomatitis virus. Cancer Res 2007; 67(6): 2840–2848

[21] Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov 2016; 15(9): 660

[22] Taguchi S, Fukuhara H, Todo T. Oncolytic virus therapy in Japan: progress in clinical trials and future perspectives. Jpn J Clin Oncol 2019; 49(3): 201–209

[23] Guo L, Hu C, Liu Y, Chen X, Song D, Shen R, Liu Z, Jia X, Zhang Q, Gao Y, Deng Z, Zuo T, Hu J, Zhu W, Cai J, Yan G, Liang J, Lin Y. Directed natural evolution generates a next-generation oncolytic virus with a high potency and safety profile. Nat Commun 2023; 14(1): 3410

[24] Takano G, Esaki S, Goshima F, Enomoto A, Hatano Y, Ozaki H, Watanabe T, Sato Y, Kawakita D, Murakami S, Murata T, Nishiyama Y, Iwasaki S, Kimura H. Oncolytic activity of naturally attenuated herpes-simplex virus HF10 against an immunocompetent model of oral carcinoma. Mol Ther Oncolytics 2020; 20: 220–227

[25] Garmaroudi GA, Karimi F, Naeini LG, Kokabian P, Givtaj N. Therapeutic efficacy of oncolytic viruses in fighting cancer: recent advances and perspective. Oxid Med Cell Longev 2022; 2022: 3142306

[26] Robilotti E, Zeitouni NC, Orloff M. Biosafety and biohazard considerations of HSV-1-based oncolytic viral immunotherapy. Front Mol Biosci 2023; 10: 1178382

[27] Liu H, Luo H. Development of group B coxsackievirus as an oncolytic virus: opportunities and challenges. Viruses 2021; 13(6): 1082

[28] Jayawardena N, Poirier JT, Burga LN, Bostina M. Virus-receptor interactions and virus neutralization: insights for oncolytic virus development. Oncolytic Virother 2020; 9: 1–15

[29] Chaurasiya S, Chen NG, Fong Y. Oncolytic viruses and immunity. Curr Opin Immunol 2018; 51: 83–90

[30] Tian Y, Xie D, Yang L. Engineering strategies to enhance oncolytic viruses in cancer immunotherapy. Signal Transduct Target Ther 2022; 7(1): 117

[31] Jeong SN, Yoo SY. Novel oncolytic virus armed with cancer suicide gene and normal vasculogenic gene for improved anti-tumor activity. Cancers (Basel) 2020; 12(5): 1070

[32] Chiocca EA, Rabkin SD. Oncolytic viruses and their application to cancer immunotherapy. Cancer Immunol Res 2014; 2(4): 295–300

[33] Gong J, Sachdev E, Mita AC, Mita MM. Clinical development of reovirus for cancer therapy: an oncolytic virus with immune-mediated antitumor activity. World J Methodol 2016; 6(1): 25–42

[34] Howells A, Marelli G, Lemoine NR, Wang Y. Oncolytic viruses-interaction of virus and tumor cells in the battle to eliminate cancer. Front Oncol 2017; 7: 195

[35] Herceg Z, Hainaut P. Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis. Mol Oncol 2007; 1(1): 26–41

[36] Martin K, Schreiner J, Zippelius A. Modulation of APC function and anti-tumor immunity by anti-cancer drugs. Front Immunol 2015; 6: 501

[37] Jeong S, Park SH. Co-stimulatory receptors in cancers and their implications for cancer immunotherapy. Immune Netw 2020; 20(1): e3

[38] Huber V, Camisaschi C, Berzi A, Ferro S, Lugini L, Triulzi T, Tuccitto A, Tagliabue E, Castelli C, Rivoltini L. Cancer acidity: an ultimate frontier of tumor immune escape and a novel target of immunomodulation. Semin Cancer Biol 2017; 43: 74–89

[39] Emami Nejad A, Najafgholian S, Rostami A, Sistani A, Shojaeifar S, Esparvarinha M, Nedaeinia R, Haghjooy Javanmard S, Taherian M, Ahmadlou M, Salehi R, Sadeghi B, Manian M. The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment. Cancer Cell Int 2021; 21(1): 62

[40] Tang T, Huang X, Zhang G, Hong Z, Bai X, Liang T. Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy. Signal Transduct Target Ther 2021; 6(1): 72

[41] Tie Y, Tang F, Wei YQ, Wei XW. Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets. J Hematol Oncol 2022; 15(1): 61

[42] Jin MZ, Jin WL. The updated landscape of tumor microenvironment and drug repurposing. Signal Transduct Target Ther 2020; 5(1): 166

[43] Prasad S, Saha P, Chatterjee B, Chaudhary AA, Lall R, Srivastava AK. Complexity of tumor microenvironment: therapeutic role of curcumin and its metabolites. Nutr Cancer 2023; 75(1): 1–13

[44] Patsoukis N, Wang Q, Strauss L, Boussiotis VA. Revisiting the PD-1 pathway. Sci Adv 2020; 6(38): eabd2712

[45] Labani-Motlagh A, Ashja-Mahdavi M, Loskog A. The tumor microenvironment: a milieu hindering and obstructing antitumor immune responses. Front Immunol 2020; 11: 940

[46] Giraldo NA, Sanchez-Salas R, Peske JD, Vano Y, Becht E, Petitprez F, Validire P, Ingels A, Cathelineau X, Fridman WH, Sautès-Fridman C. The clinical role of the TME in solid cancer. Br J Cancer 2019; 120(1): 45–53

[47] Dhatchinamoorthy K, Colbert JD, Rock KL. Cancer immune evasion through loss of MHC class I antigen presentation. Front Immunol 2021; 12: 636568

[48] Klement JD, Redd PS, Lu C, Merting AD, Poschel DB, Yang D, Savage NM, Zhou G, Munn DH, Fallon PG, Liu K. Tumor PD-L1 engages myeloid PD-1 to suppress type I interferon to impair cytotoxic T lymphocyte recruitment. Cancer Cell 2023; 41(3): 620–636.e9

[49] Beatty GL, Gladney WL. Immune escape mechanisms as a guide for cancer immunotherapy. Clin Cancer Res 2015; 21(4): 687–692

[50] Ban Y, Mai J, Li X, Mitchell-Flack M, Zhang T, Zhang L, Chouchane L, Ferrari M, Shen H, Ma X. Targeting autocrine CCL5-CCR5 axis reprograms immunosuppressive myeloid cells and reinvigorates antitumor immunity. Cancer Res 2017; 77(11): 2857–2868

[51] Melese ES, Franks E, Cederberg RA, Harbourne BT, Shi R, Wadsworth BJ, Collier JL, Halvorsen EC, Johnson F, Luu J, Oh MH, Lam V, Krystal G, Hoover SB, Raffeld M, Simpson RM, Unni AM, Lam WL, Lam S, Abraham N, Bennewith KL, Lockwood WW. CCL5 production in lung cancer cells leads to an altered immune microenvironment and promotes tumor development. OncoImmunology 2021; 11(1): 2010905

[52] O’Garra A, Vieira PL, Vieira P, Goldfeld AE. IL-10-producing and naturally occurring CD4⁺ Tregs: limiting collateral damage. J Clin Invest 2004; 114(10): 1372–1378

[53] Holmgaard RB, Zamarin D, Li Y, Gasmi B, Munn DH, Allison JP, Merghoub T, Wolchok JD. Tumor-expressed IDO recruits and activates MDSCs in a Treg-dependent manner. Cell Rep 2015; 13(2): 412–424

[54] Ma N, Liu Q, Hou L, Wang Y, Liu Z. MDSCs are involved in the protumorigenic potentials of GM-CSF in colitis-associated cancer. Int J Immunopathol Pharmacol 2017; 30(2): 152–162

[55] Gratchev A. TGF-β signalling in tumour associated macrophages. Immunobiology 2017; 222(1): 75–81

[56] Polanczyk MJ, Walker E, Haley D, Guerrouahen BS, Akporiaye ET. Blockade of TGF-β signaling to enhance the antitumor response is accompanied by dysregulation of the functional activity of CD4⁺CD25⁺Foxp3⁺ and CD4⁺CD25^-Foxp3⁺ T cells. J Transl Med 2019; 17(1): 219

[57] Kim SK, Cho SW. The evasion mechanisms of cancer immunity and drug intervention in the tumor microenvironment. Front Pharmacol 2022; 13: 868695

[58] Chen J, Zhao D, Zhang L, Zhang J, Xiao Y, Wu Q, Wang Y, Zhan Q. Tumor-associated macrophage (TAM)-derived CCL22 induces FAK addiction in esophageal squamous cell carcinoma (ESCC). Cell Mol Immunol 2022; 19(9): 1054–1066

[59] Rapp M, Wintergerst MWM, Kunz WG, Vetter VK, Knott MML, Lisowski D, Haubner S, Moder S, Thaler R, Eiber S, Meyer B, Röhrle N, Piseddu I, Grassmann S, Layritz P, Kühnemuth B, Stutte S, Bourquin C, von Andrian UH, Endres S, Anz D. CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes. J Exp Med 2019; 216(5): 1170–1181

[60] Balta E, Wabnitz GH, Samstag Y. Hijacked immune cells in the tumor microenvironment: molecular mechanisms of immunosuppression and cues to improve T cell-based immunotherapy of solid tumors. Int J Mol Sci 2021; 22(11): 5736

[61] Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol 2020; 20(11): 651–668

[62] Kartikasari AER, Prakash MD, Cox M, Wilson K, Boer JC, Cauchi JA, Plebanski M. Therapeutic cancer vaccines—T cell responses and epigenetic modulation. Front Immunol 2019; 9: 3109

[63] Morse MA, Gwin WR 3rd, Mitchell DA. Vaccine therapies for cancer: then and now. Target Oncol 2021; 16(2): 121–152

[64] Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J 2021; 11(4): 69

[65] To V, Evtimov VJ, Jenkin G, Pupovac A, Trounson AO, Boyd RL. CAR-T cell development for cutaneous T cell lymphoma: current limitations and potential treatment strategies. Front Immunol 2022; 13: 968395

[66] Shafer P, Kelly LM, Hoyos V. Cancer therapy with TCR-engineered T cells: current strategies, challenges, and prospects. Front Immunol 2022; 13: 835762

[67] Baulu E, Gardet C, Chuvin N, Depil S. TCR-engineered T cell therapy in solid tumors: state of the art and perspectives. Sci Adv 2023; 9(7): eadf3700

[68] Zappasodi R, Merghoub T, Wolchok JD. Emerging concepts for immune checkpoint blockade-based combination therapies. Cancer Cell 2018; 33(4): 581–598

[69] Samnani S, Sachedina F, Gupta M, Guo E, Navani V. Mechanisms and clinical implications in renal carcinoma resistance: narrative review of immune checkpoint inhibitors. Cancer Drug Resist 2023; 6(2): 416–429

[70] Wang DR, Wu XL, Sun YL. Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response. Signal Transduct Target Ther 2022; 7(1): 331

[71] Zhou Z, Tao C, Li J, Tang JC, Chan AS, Zhou Y. Chimeric antigen receptor T cells applied to solid tumors. Front Immunol 2022; 13: 984864

[72] Farhood B, Najafi M, Mortezaee K. CD8⁺ cytotoxic T lymphocytes in cancer immunotherapy: a review. J Cell Physiol 2019; 234(6): 8509–8521

[73] Liu YT, Sun ZJ. Turning cold tumors into hot tumors by improving T-cell infiltration. Theranostics 2021; 11(11): 5365–5386

[74] Bonaventura P, Shekarian T, Alcazer V, Valladeau-Guilemond J, Valsesia-Wittmann S, Amigorena S, Caux C, Depil S. Cold tumors: a therapeutic challenge for immunotherapy. Front Immunol 2019; 10: 168

[75] Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov 2019; 18(3): 197–218

[76] Duan Q, Zhang H, Zheng J, Zhang L. Turning cold into hot: firing up the tumor microenvironment. Trends Cancer 2020; 6(7): 605–618

[77] Ganesh K. Optimizing immunotherapy for colorectal cancer. Nat Rev Gastroenterol Hepatol 2022; 19(2): 93–94

[78] Wang Y, Liang Y, Xu H, Zhang X, Mao T, Cui J, Yao J, Wang Y, Jiao F, Xiao X, Hu J, Xia Q, Zhang X, Wang X, Sun Y, Fu D, Shen L, Xu X, Xue J, Wang L. Single-cell analysis of pancreatic ductal adenocarcinoma identifies a novel fibroblast subtype associated with poor prognosis but better immunotherapy response. Cell Discov 2021; 7(1): 36

[79] Zheng Z, Wieder T, Mauerer B, Schäfer L, Kesselring R, Braumüller H. T cells in colorectal cancer: unravelling the function of different T cell subsets in the tumor microenvironment. Int J Mol Sci 2023; 24(14): 11673

[80] Narayanan S, Vicent S, Ponz-Sarvisé M. PDAC as an immune evasive disease: can 3D model systems aid to tackle this clinical problem?. Front Cell Dev Biol 2021; 9: 787249

[81] Dutta R, Khalil R, Mayilsamy K, Green R, Howell M, Bharadwaj S, Mohapatra SS, Mohapatra S. Combination therapy of mithramycin A and immune checkpoint inhibitor for the treatment of colorectal cancer in an orthotopic murine model. Front Immunol 2021; 12: 706133

[82] Jeong KY. Challenges to addressing the unmet medical needs for immunotherapy targeting cold colorectal cancer. World J Gastrointest Oncol 2023; 15(2): 215–224

[83] Liu JL, Yang M, Bai JG, Liu Z, Wang XS. “Cold” colorectal cancer faces a bottleneck in immunotherapy. World J Gastrointest Oncol 2023; 15(2): 240–250

[84] Fabian KP, Wolfson B, Hodge JW. From immunogenic cell death to immunogenic modulation: select chemotherapy regimens induce a spectrum of immune-enhancing activities in the tumor microenvironment. Front Oncol 2021; 11: 728018

[85] Mihm S. Danger-associated molecular patterns (DAMPs): molecular triggers for sterile inflammation in the liver. Int J Mol Sci 2018; 19(10): 3104

[86] Fucikova J, Kepp O, Kasikova L, Petroni G, Yamazaki T, Liu P, Zhao L, Spisek R, Kroemer G, Galluzzi L. Detection of immunogenic cell death and its relevance for cancer therapy. Cell Death Dis 2020; 11(11): 1013

[87] Guo ZS, Liu Z, Bartlett DL. Oncolytic immunotherapy: dying the right way is a key to eliciting potent antitumor immunity. Front Oncol 2014; 4: 74

[88] Garg AD, Agostinis P. Cell death and immunity in cancer: from danger signals to mimicry of pathogen defense responses. Immunol Rev 2017; 280(1): 126–148

[89] Asadzadeh Z, Safarzadeh E, Safaei S, Baradaran A, Mohammadi A, Hajiasgharzadeh K, Derakhshani A, Argentiero A, Silvestris N, Baradaran B. Current approaches for combination therapy of cancer: the role of immunogenic cell death. Cancers (Basel) 2020; 12(4): 1047

[90] Ramírez-Labrada A, Pesini C, Santiago L, Hidalgo S, Calvo-Pérez A, Oñate C, Andrés-Tovar A, Garzón-Tituaña M, Uranga-Murillo I, Arias MA, Galvez EM, Pardo J. All about (NK cell-mediated) death in two acts and an unexpected encore: initiation, execution and activation of adaptive immunity. Front Immunol 2022; 13: 896228

[91] Zhu J, Huang X, Yang Y. A critical role for type I IFN-dependent NK cell activation in innate immune elimination of adenoviral vectors in vivo. Mol Ther 2008; 16(7): 1300–1307

[92] Aaes TL, Kaczmarek A, Delvaeye T, De Craene B, De Koker S, Heyndrickx L, Delrue I, Taminau J, Wiernicki B, De Groote P, Garg AD, Leybaert L, Grooten J, Bertrand MJ, Agostinis P, Berx G, Declercq W, Vandenabeele P, Krysko DV. Vaccination with necroptotic cancer cells induces efficient anti-tumor immunity. Cell Rep 2016; 15(2): 274–287

[93] Workenhe ST, Mossman KL. Oncolytic virotherapy and immunogenic cancer cell death: sharpening the sword for improved cancer treatment strategies. Mol Ther 2014; 22(2): 251–256

[94] Crupi MJF, Taha Z, Janssen TJA, Petryk J, Boulton S, Alluqmani N, Jirovec A, Kassas O, Khan ST, Vallati S, Lee E, Huang BZ, Huh M, Pikor L, He X, Marius R, Austin B, Duong J, Pelin A, Neault S, Azad T, Breitbach CJ, Stojdl DF, Burgess MF, McComb S, Auer R, Diallo JS, Ilkow CS, Bell JC. Oncolytic virus driven T-cell-based combination immunotherapy platform for colorectal cancer. Front Immunol 2022; 13: 1029269

[95] Ye K, Li F, Wang R, Cen T, Liu S, Zhao Z, Li R, Xu L, Zhang G, Xu Z, Deng L, Li L, Wang W, Stepanov A, Wan Y, Guo Y, Li Y, Wang Y, Tian Y, Gabibov AG, Yan Y, Zhang H. An armed oncolytic virus enhances the efficacy of tumor-infiltrating lymphocyte therapy by converting tumors to artificial antigen-presenting cells in situ. Mol Ther 2022; 30(12): 3658–3676

[96] Wang G, Kang X, Chen KS, Jehng T, Jones L, Chen J, Huang XF, Chen SY. An engineered oncolytic virus expressing PD-L1 inhibitors activates tumor neoantigen-specific T cell responses. Nat Commun 2020; 11(1): 1395

[97] Packiriswamy N, Upreti D, Zhou Y, Khan R, Miller A, Diaz RM, Rooney CM, Dispenzieri A, Peng KW, Russell SJ. Oncolytic measles virus therapy enhances tumor antigen-specific T-cell responses in patients with multiple myeloma. Leukemia 2020; 34(12): 3310–3322

[98] Ma J, Ramachandran M, Jin C, Quijano-Rubio C, Martikainen M, Yu D, Essand M. Characterization of virus-mediated immunogenic cancer cell death and the consequences for oncolytic virus-based immunotherapy of cancer. Cell Death Dis 2020; 11(1): 48

[99] Ma R, Li Z, Chiocca EA, Caligiuri MA, Yu J. The emerging field of oncolytic virus-based cancer immunotherapy. Trends Cancer 2023; 9(2): 122–139

[100] Niavarani SR, Lawson C, Boudaud M, Simard C, Tai LH. Oncolytic vesicular stomatitis virus-based cellular vaccine improves triple-negative breast cancer outcome by enhancing natural killer and CD8⁺ T-cell functionality. J Immunother Cancer 2020; 8(1): e000465

[101] Veglia F, Gabrilovich DI. Dendritic cells in cancer: the role revisited. Curr Opin Immunol 2017; 45: 43–51

[102] Sadeghzadeh M, Bornehdeli S, Mohahammadrezakhani H, Abolghasemi M, Poursaei E, Asadi M, Zafari V, Aghebati-Maleki L, Shanehbandi D. Dendritic cell therapy in cancer treatment; the state-of-the-art. Life Sci 2020; 254: 117580

[103] Bak SP, Barnkob MS, Bai A, Higham EM, Wittrup KD, Chen J. Differential requirement for CD70 and CD80/CD86 in dendritic cell-mediated activation of tumor-tolerized CD8 T cells. J Immunol 2012; 189(4): 1708–1716

[104] Ke N, Su A, Huang W, Szatmary P, Zhang Z. Regulating the expression of CD80/CD86 on dendritic cells to induce immune tolerance after xeno-islet transplantation. Immunobiology 2016; 221(7): 803–812

[105] Kim HW, Cho SI, Bae S, Kim H, Kim Y, Hwang YI, Kang JS, Lee WJ, Vitamin C. Vitamin C up-regulates expression of CD80, CD86 and MHC class II on dendritic cell line, DC-1 via the activation of p38 MAPK. Immune Netw 2012; 12(6): 277–283

[106] Calmeiro J, Carrascal MA, Tavares AR, Ferreira DA, Gomes C, Falcão A, Cruz MT, Neves BM. Dendritic cell vaccines for cancer immunotherapy: the role of human conventional type 1 dendritic cells. Pharmaceutics 2020; 12(2): 158

[107] Marciscano AE, Anandasabapathy N. The role of dendritic cells in cancer and anti-tumor immunity. Semin Immunol 2021; 52: 101481

[108] Perez CR, De Palma M. Engineering dendritic cell vaccines to improve cancer immunotherapy. Nat Commun 2019; 10(1): 5408

[109] Ding Z, Li Q, Zhang R, Xie L, Shu Y, Gao S, Wang P, Su X, Qin Y, Wang Y, Fang J, Zhu Z, Xia X, Wei G, Wang H, Qian H, Guo X, Gao Z, Wang Y, Wei Y, Xu Q, Xu H, Yang L. Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer. Signal Transduct Target Ther 2021; 6(1): 26

[110] Sabado RL, Balan S, Bhardwaj N. Dendritic cell-based immunotherapy. Cell Res 2017; 27(1): 74–95

[111] Ma Y, Chen M, Jin H, Prabhakar BS, Valyi-Nagy T, He B. An engineered herpesvirus activates dendritic cells and induces protective immunity. Sci Rep 2017; 7(1): 41461

[112] Pidelaserra-Martí G, Engeland CE. Mechanisms of measles virus oncolytic immunotherapy. Cytokine Growth Factor Rev 2020; 56: 28–38

[113] Liu W, Wang X, Feng X, Yu J, Liu X, Jia X, Zhang H, Wu H, Wang C, Wu J, Yu B, Yu X. Oncolytic adenovirus-mediated intratumoral expression of TRAIL and CD40L enhances immunotherapy by modulating the tumor microenvironment in immunocompetent mouse models. Cancer Lett 2022; 535: 215661

[114] Hamilton JA. GM-CSF-dependent inflammatory pathways. Front Immunol 2019; 10: 2055

[115] Rangsitratkul C, Lawson C, Bernier-Godon F, Niavarani SR, Boudaud M, Rouleau S, Gladu-Corbin AO, Surendran A, Ekindi-Ndongo N, Koti M, Ilkow CS, Richard PO, Tai LH. Intravesical immunotherapy with a GM-CSF armed oncolytic vesicular stomatitis virus improves outcome in bladder cancer. Mol Ther Oncolytics 2022; 24: 507–521

[116] Kaufman HL, Shalhout SZ, Iodice G. Talimogene laherparepvec: moving from first-in-class to best-in-class. Front Mol Biosci 2022; 9: 834841

[117] Ghouse SM, Nguyen HM, Bommareddy PK, Guz-Montgomery K, Saha D. Oncolytic herpes simplex virus encoding IL12 controls triple-negative breast cancer growth and metastasis. Front Oncol 2020; 10: 384

[118] Haghighi-Najafabadi N, Roohvand F, Shams Nosrati MS, Teimoori-Toolabi L, Azadmanesh K. Oncolytic herpes simplex virus type-1 expressing IL-12 efficiently replicates and kills human colorectal cancer cells. Microb Pathog 2021; 160: 105164

[119] Zafar S, Sorsa S, Siurala M, Hemminki O, Havunen R, Cervera-Carrascon V, Santos JM, Wang H, Lieber A, De Gruijl T, Kanerva A, Hemminki A. CD40L coding oncolytic adenovirus allows long-term survival of humanized mice receiving dendritic cell therapy. OncoImmunology 2018; 7(10): e1490856

[120] Wang R, Chen J, Wang W, Zhao Z, Wang H, Liu S, Li F, Wan Y, Yin J, Wang R, Li Y, Zhang C, Zhang H, Cao Y. CD40L-armed oncolytic herpes simplex virus suppresses pancreatic ductal adenocarcinoma by facilitating the tumor microenvironment favorable to cytotoxic T cell response in the syngeneic mouse model. J Immunother Cancer 2022; 10(1): e003809

[121] Bommareddy PK, Aspromonte S, Zloza A, Rabkin SD, Kaufman HL. MEK inhibition enhances oncolytic virus immunotherapy through increased tumor cell killing and T cell activation. Sci Transl Med 2018; 10(471): eaau0417

[122] Gettinger S, Choi J, Hastings K, Truini A, Datar I, Sowell R, Wurtz A, Dong W, Cai G, Melnick MA, Du VY, Schlessinger J, Goldberg SB, Chiang A, Sanmamed MF, Melero I, Agorreta J, Montuenga LM, Lifton R, Ferrone S, Kavathas P, Rimm DL, Kaech SM, Schalper K, Herbst RS, Politi K. Impaired HLA class I antigen processing and presentation as a mechanism of acquired resistance to immune checkpoint inhibitors in lung cancer. Cancer Discov 2017; 7(12): 1420–1435

[123] D’Alise AM, Leoni G, Cotugno G, Troise F, Langone F, Fichera I, De Lucia M, Avalle L, Vitale R, Leuzzi A, Bignone V, Di Matteo E, Tucci FG, Poli V, Lahm A, Catanese MT, Folgori A, Colloca S, Nicosia A, Scarselli E. Adenoviral vaccine targeting multiple neoantigens as strategy to eradicate large tumors combined with checkpoint blockade. Nat Commun 2019; 10(1): 2688

[124] Das K, Belnoue E, Rossi M, Hofer T, Danklmaier S, Nolden T, Schreiber LM, Angerer K, Kimpel J, Hoegler S, Spiesschaert B, Kenner L, von Laer D, Elbers K, Derouazi M, Wollmann G. A modular self-adjuvanting cancer vaccine combined with an oncolytic vaccine induces potent antitumor immunity. Nat Commun 2021; 12(1): 5195

[125] Maimela NR, Liu S, Zhang Y. Fates of CD8⁺ T cells in tumor microenvironment. Comput Struct Biotechnol J 2018; 17: 1–13

[126] Spranger S, Dai D, Horton B, Gajewski TF. Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell 2017; 31(5): 711–723.e4

[127] van Vloten JP, Matuszewska K, Minow MAA, Minott JA, Santry LA, Pereira M, Stegelmeier AA, McAusland TM, Klafuric EM, Karimi K, Colasanti J, McFadden DG, Petrik JJ, Bridle BW, Wootton SK. Oncolytic Orf virus licenses NK cells via cDC1 to activate innate and adaptive antitumor mechanisms and extends survival in a murine model of late-stage ovarian cancer. J Immunother Cancer 2022; 10(3): e004335

[128] Cervera-Carrascon V, Quixabeira DCA, Santos JM, Havunen R, Zafar S, Hemminki O, Heiniö C, Munaro E, Siurala M, Sorsa S, Mirtti T, Järvinen P, Mildh M, Nisen H, Rannikko A, Anttila M, Kanerva A, Hemminki A. Tumor microenvironment remodeling by an engineered oncolytic adenovirus results in improved outcome from PD-L1 inhibition. OncoImmunology 2020; 9(1): 1761229

[129] Eckert EC, Nace RA, Tonne JM, Evgin L, Vile RG, Russell SJ. Generation of a tumor-specific chemokine gradient using oncolytic vesicular stomatitis virus encoding CXCL9. Mol Ther Oncolytics 2019; 16: 63–74

[130] Lee JH, Shklovskaya E, Lim SY, Carlino MS, Menzies AM, Stewart A, Pedersen B, Irvine M, Alavi S, Yang JYH, Strbenac D, Saw RPM, Thompson JF, Wilmott JS, Scolyer RA, Long GV, Kefford RF, Rizos H. Transcriptional downregulation of MHC class I and melanoma de-differentiation in resistance to PD-1 inhibition. Nat Commun 2020; 11(1): 1897

[131] Jugovic P, Hill AM, Tomazin R, Ploegh H, Johnson DC. Inhibition of major histocompatibility complex class I antigen presentation in pig and primate cells by herpes simplex virus type 1 and 2 ICP47. J Virol 1998; 72(6): 5076–5084

[132] Gujar SA, Pan DA, Marcato P, Garant KA, Lee PW. Oncolytic virus-initiated protective immunity against prostate cancer. Mol Ther 2011; 19(4): 797–804

[133] Paul S, Lal G. The molecular mechanism of natural killer cells function and its importance in cancer immunotherapy. Front Immunol 2017; 8: 1124

[134] Myers JA, Miller JS. Exploring the NK cell platform for cancer immunotherapy. Nat Rev Clin Oncol 2021; 18(2): 85–100

[135] Shemesh A, Pickering H, Roybal KT, Lanier LL. Differential IL-12 signaling induces human natural killer cell activating receptor-mediated ligand-specific expansion. J Exp Med 2022; 219(8): e20212434

[136] Souza-Fonseca-Guimaraes F, Young A, Mittal D, Martinet L, Bruedigam C, Takeda K, Andoniou CE, Degli-Esposti MA, Hill GR, Smyth MJ. NK cells require IL-28R for optimal in vivo activity. Proc Natl Acad Sci USA 2015; 112(18): E2376–E2384

[137] Hamdan F, Ylösmäki E, Chiaro J, Giannoula Y, Long M, Fusciello M, Feola S, Martins B, Feodoroff M, Antignani G, Russo S, Kari O, Lee M, Järvinen P, Nisen H, Kreutzman A, Leusen J, Mustjoki S, McWilliams TG, Grönholm M, Cerullo V. Novel oncolytic adenovirus expressing enhanced cross-hybrid IgGA Fc PD-L1 inhibitor activates multiple immune effector populations leading to enhanced tumor killing in vitro, in vivo and with patient-derived tumor organoids. J Immunother Cancer 2021; 9(8): e003000

[138] Xu B, Tian L, Chen J, Wang J, Ma R, Dong W, Li A, Zhang J, Antonio Chiocca E, Kaur B, Feng M, Caligiuri MA, Yu J. An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma. Nat Commun 2021; 12(1): 5908

[139] Niemann J, Woller N, Brooks J, Fleischmann-Mundt B, Martin NT, Kloos A, Knocke S, Ernst AM, Manns MP, Kubicka S, Wirth TC, Gerardy-Schahn R, Kühnel F. Molecular retargeting of antibodies converts immune defense against oncolytic viruses into cancer immunotherapy. Nat Commun 2019; 10(1): 3236

[140] Yang Q, Guo N, Zhou Y, Chen J, Wei Q, Han M. The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy. Acta Pharm Sin B 2020; 10(11): 2156–2170

[141] Zhu S, Yi M, Wu Y, Dong B, Wu K. Roles of tumor-associated macrophages in tumor progression: implications on therapeutic strategies. Exp Hematol Oncol 2021; 10(1): 60

[142] Wang J, Li D, Cang H, Guo B. Crosstalk between cancer and immune cells: role of tumor-associated macrophages in the tumor microenvironment. Cancer Med 2019; 8(10): 4709–4721

[143] Muñoz-Rojas AR, Kelsey I, Pappalardo JL, Chen M, Miller-Jensen K. Co-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cells. Nat Commun 2021; 12(1): 301

[144] Müller E, Christopoulos PF, Halder S, Lunde A, Beraki K, Speth M, Øynebråten I, Corthay A. Toll-like receptor ligands and interferon-γ synergize for induction of antitumor M1 macrophages. Front Immunol 2017; 8: 1383

[145] Pan Y, Yu Y, Wang X, Zhang T. Tumor-associated macrophages in tumor immunity. Front Immunol 2020; 11: 583084

[146] Lin C, Ren W, Luo Y, Li S, Chang Y, Li L, Xiong D, Huang X, Xu Z, Yu Z, Wang Y, Zhang J, Huang C, Xia N. Intratumoral delivery of a PD-1-blocking scFv encoded in oncolytic HSV-1 promotes antitumor immunity and synergizes with TIGIT blockade. Cancer Immunol Res 2020; 8(5): 632–647

[147] Cao F, Nguyen P, Hong B, DeRenzo C, Rainusso NC, Rodriguez Cruz T, Wu MF, Liu H, Song XT, Suzuki M, Wang LL, Yustein JT, Gottschalk S. Engineering oncolytic vaccinia virus to redirect macrophages to tumor cells. Adv Cell Gene Ther 2021; 4(2): e99

[148] Bruno A, Mortara L, Baci D, Noonan DM, Albini A. Myeloid derived suppressor cells interactions with natural killer cells and pro-angiogenic activities: roles in tumor progression. Front Immunol 2019; 10: 771

[149] Cheng JN, Yuan YX, Zhu B, Jia Q. Myeloid-derived suppressor cells: a multifaceted accomplice in tumor progression. Front Cell Dev Biol 2021; 9: 740827

[150] Wu H, Li SS, Zhou M, Jiang AN, He Y, Wang S, Yang W, Liu H. Palliative radiofrequency ablation accelerates the residual tumor progression through increasing tumor-infiltrating MDSCs and reducing T-cell-mediated anti-tumor immune responses in animal model. Front Oncol 2020; 10: 1308

[151] Chen Y, Xu Y, Zhao H, Zhou Y, Zhang J, Lei J, Wu L, Zhou M, Wang J, Yang S, Zhang X, Yan G, Li Y. Myeloid-derived suppressor cells deficient in cholesterol biosynthesis promote tumor immune evasion. Cancer Lett 2023; 564: 216208

[152] Li K, Shi H, Zhang B, Ou X, Ma Q, Chen Y, Shu P, Li D, Wang Y. Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer. Signal Transduct Target Ther 2021; 6(1): 362

[153] Tomić S, Joksimović B, Bekić M, Vasiljević M, Milanović M, Čolić M, Vučević D. Prostaglanin-E2 potentiates the suppressive functions of human mononuclear myeloid-derived suppressor cells and increases their capacity to expand IL-10-producing regulatory T cell subsets. Front Immunol 2019; 10: 475

[154] Tan Z, Liu L, Chiu MS, Cheung KW, Yan CW, Yu Z, Lee BK, Liu W, Man K, Chen Z. Virotherapy-recruited PMN-MDSC infiltration of mesothelioma blocks antitumor CTL by IL-10-mediated dendritic cell suppression. OncoImmunology 2018; 8(1): e1518672

[155] Otani Y, Yoo JY, Lewis CT, Chao S, Swanner J, Shimizu T, Kang JM, Murphy SA, Rivera-Caraballo K, Hong B, Glorioso JC, Nakashima H, Lawler SE, Banasavadi-Siddegowda Y, Heiss JD, Yan Y, Pei G, Caligiuri MA, Zhao Z, Chiocca EA, Yu J, Kaur B. NOTCH-induced MDSC recruitment after oHSV virotherapy in CNS cancer models modulates antitumor immunotherapy. Clin Cancer Res 2022; 28(7): 1460–1473

[156] Hou W, Sampath P, Rojas JJ, Thorne SH. Oncolytic virus-mediated targeting of PGE2 in the tumor alters the immune status and sensitizes established and resistant tumors to immunotherapy. Cancer Cell 2016; 30(1): 108–119

[157] Rocamora-Reverte L, Melzer FL, Würzner R, Weinberger B. The complex role of regulatory T cells in immunity and aging. Front Immunol 2021; 11: 616949

[158] Yano H, Andrews LP, Workman CJ, Vignali DAA. Intratumoral regulatory T cells: markers, subsets and their impact on anti-tumor immunity. Immunology 2019; 157(3): 232–247

[159] Tanaka A, Sakaguchi S. Targeting Treg cells in cancer immunotherapy. Eur J Immunol 2019; 49(8): 1140–1146

[160] González-Navajas JM, Fan DD, Yang S, Yang FM, Lozano-Ruiz B, Shen L, Lee J. The impact of Tregs on the anticancer immunity and the efficacy of immune checkpoint inhibitor therapies. Front Immunol 2021; 12: 625783

[161] Zammarchi F, Havenith K, Bertelli F, Vijayakrishnan B, Chivers S, van Berkel PH. CD25-targeted antibody-drug conjugate depletes regulatory T cells and eliminates established syngeneic tumors via antitumor immunity. J Immunother Cancer 2020; 8(2): e000860

[162] Solomon I, Amann M, Goubier A, Arce Vargas F, Zervas D, Qing C, Henry JY, Ghorani E, Akarca AU, Marafioti T, Śledzińska A, Werner Sunderland M, Franz Demane D, Clancy JR, Georgiou A, Salimu J, Merchiers P, Brown MA, Flury R, Eckmann J, Murgia C, Sam J, Jacobsen B, Marrer-Berger E, Boetsch C, Belli S, Leibrock L, Benz J, Koll H, Sutmuller R, Peggs KS, Quezada SA. CD25-T_reg-depleting antibodies preserving IL-2 signaling on effector T cells enhance effector activation and antitumor immunity. Nat Cancer 2020; 1(12): 1153–1166

[163] Sugawara K, Iwai M, Ito H, Tanaka M, Seto Y, Todo T. Oncolytic herpes virus G47Δ works synergistically with CTLA-4 inhibition via dynamic intratumoral immune modulation. Mol Ther Oncolytics 2021; 22: 129–142

[164] Moon LD, Asher RA, Fawcett JW. Limited growth of severed CNS axons after treatment of adult rat brain with hyaluronidase. J Neurosci Res 2003; 71(1): 23–37

[165] Ramanujan S, Pluen A, McKee TD, Brown EB, Boucher Y, Jain RK. Diffusion and convection in collagen gels: implications for transport in the tumor interstitium. Biophys J 2002; 83(3): 1650–1660

[166] Pires A, Greenshields-Watson A, Jones E, Smart K, Lauder SN, Somerville M, Milutinovic S, Kendrick H, Hindley JP, French R, Smalley MJ, Watkins WJ, Andrews R, Godkin A, Gallimore A. Immune remodeling of the extracellular matrix drives loss of cancer stem cells and tumor rejection. Cancer Immunol Res 2020; 8(12): 1520–1531

[167] Pibuel MA, Poodts D, Díaz M, Hajos SE, Lompardía SL. The scrambled story between hyaluronan and glioblastoma. J Biol Chem 2021; 296: 100549

[168] Kiyokawa J, Kawamura Y, Ghouse SM, Acar S, Barçın E, Martínez-Quintanilla J, Martuza RL, Alemany R, Rabkin SD, Shah K, Wakimoto H. Modification of extracellular matrix enhances oncolytic adenovirus immunotherapy in glioblastoma. Clin Cancer Res 2021; 27(3): 889–902

[169] Kim JH, Lee YS, Kim H, Huang JH, Yoon AR, Yun CO. Relaxin expression from tumor-targeting adenoviruses and its intratumoral spread, apoptosis induction, and efficacy. J Natl Cancer Inst 2006; 98(20): 1482–1493

[170] Jung BK, Ko HY, Kang H, Hong J, Ahn HM, Na Y, Kim H, Kim JS, Yun CO. Relaxin-expressing oncolytic adenovirus induces remodeling of physical and immunological aspects of cold tumor to potentiate PD-1 blockade. J Immunother Cancer 2020; 8(2): e000763

[171] Quintero-Fabián S, Arreola R, Becerril-Villanueva E, Torres-Romero JC, Arana-Argáez V, Lara-Riegos J, Ramírez-Camacho MA, Alvarez-Sánchez ME. Role of matrix metalloproteinases in angiogenesis and cancer. Front Oncol 2019; 9: 1370

[172] Page-McCaw A, Ewald AJ, Werb Z. Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 2007; 8(3): 221–233

[173] Gobin E, Bagwell K, Wagner J, Mysona D, Sandirasegarane S, Smith N, Bai S, Sharma A, Schleifer R, She JX. A pan-cancer perspective of matrix metalloproteases (MMP) gene expression profile and their diagnostic/prognostic potential. BMC Cancer 2019; 19(1): 581

[174] Huang JF, Du WX, Chen JJ. Elevated expression of matrix metalloproteinase-3 in human osteosarcoma and its association with tumor metastasis. J BUON 2016; 21(5): 1279–1286

[175] Mehner C, Miller E, Nassar A, Bamlet WR, Radisky ES, Radisky DC. Tumor cell expression of MMP3 as a prognostic factor for poor survival in pancreatic, pulmonary, and mammary carcinoma. Genes Cancer 2015; 6(11–12): 480–489

[176] Liang M, Wang J, Wu C, Wu M, Hu J, Dai J, Ruan H, Xiong S, Dong C. Targeting matrix metalloproteinase MMP3 greatly enhances oncolytic virus mediated tumor therapy. Transl Oncol 2021; 14(12): 101221

[177] Mok W, Boucher Y, Jain RK. Matrix metalloproteinases-1 and -8 improve the distribution and efficacy of an oncolytic virus. Cancer Res 2007; 67(22): 10664–10668

[178] Hong CS, Fellows W, Niranjan A, Alber S, Watkins S, Cohen JB, Glorioso JC, Grandi P. Ectopic matrix metalloproteinase-9 expression in human brain tumor cells enhances oncolytic HSV vector infection. Gene Ther 2010; 17(10): 1200–1205

[179] Choi H, Moon A. Crosstalk between cancer cells and endothelial cells: implications for tumor progression and intervention. Arch Pharm Res 2018; 41(7): 711–724

[180] Breitbach CJ, De Silva NS, Falls TJ, Aladl U, Evgin L, Paterson J, Sun YY, Roy DG, Rintoul JL, Daneshmand M, Parato K, Stanford MM, Lichty BD, Fenster A, Kirn D, Atkins H, Bell JC. Targeting tumor vasculature with an oncolytic virus. Mol Ther 2011; 19(5): 886–894

[181] Hou W, Chen H, Rojas J, Sampath P, Thorne SH. Oncolytic vaccinia virus demonstrates antiangiogenic effects mediated by targeting of VEGF. Int J Cancer 2014; 135(5): 1238–1246

[182] Matuszewska K, Santry LA, van Vloten JP, AuYeung AWK, Major PP, Lawler J, Wootton SK, Bridle BW, Petrik J. Combining vascular normalization with an oncolytic virus enhances immunotherapy in a preclinical model of advanced-stage ovarian cancer. Clin Cancer Res 2019; 25(5): 1624–1638

[183] Quixabeira DCA, Zafar S, Santos JM, Cervera-Carrascon V, Havunen R, Kudling TV, Basnet S, Anttila M, Kanerva A, Hemminki A. Oncolytic adenovirus coding for a variant interleukin 2 (vIL-2) cytokine re-programs the tumor microenvironment and confers enhanced tumor control. Front Immunol 2021; 12: 674400

[184] Heiniö C, Havunen R, Santos J, de Lint K, Cervera-Carrascon V, Kanerva A, Hemminki A. TNFa and IL2 encoding oncolytic adenovirus activates pathogen and danger-associated immunological signaling. Cells 2020; 9(4): 798

[185] Ekeke CN, Russell KL, Murthy P, Guo ZS, Soloff AC, Weber D, Pan W, Lotze MT, Dhupar R. Intrapleural interleukin-2-expressing oncolytic virotherapy enhances acute antitumor effects and T-cell receptor diversity in malignant pleural disease. J Thorac Cardiovasc Surg 2022; 163(4): e313–e328

[186] Ge Y, Wang H, Ren J, Liu W, Chen L, Chen H, Ye J, Dai E, Ma C, Ju S, Guo ZS, Liu Z, Bartlett DL. Oncolytic vaccinia virus delivering tethered IL-12 enhances antitumor effects with improved safety. J Immunother Cancer 2020; 8(1): e000710

[187] Nakao S, Arai Y, Tasaki M, Yamashita M, Murakami R, Kawase T, Amino N, Nakatake M, Kurosaki H, Mori M, Takeuchi M, Nakamura T. Intratumoral expression of IL-7 and IL-12 using an oncolytic virus increases systemic sensitivity to immune checkpoint blockade. Sci Transl Med 2020; 12(526): eaax7992

[188] Nishio N, Dotti G. Oncolytic virus expressing RANTES and IL-15 enhances function of CAR-modified T cells in solid tumors. OncoImmunology 2015; 4(2): e988098

[189] Liu D, Ma J, Ding B, Zhou H. Oncolytic vaccinia virus expressing CD40L (CD40L-VV) inhibits colorectal cancer cell growth and enhances anti-tumor activity of T cells in tumor-bearing mice. Chin J Cell Mol Imm (Xibao Yu Fenzi MianYiXue ZaZhi) 2021; 37(7): 602–607 (in Chinese)

[190] Hinterberger M, Giessel R, Fiore G, Graebnitz F, Bathke B, Wennier S, Chaplin P, Melero I, Suter M, Lauterbach H, Berraondo P, Hochrein H, Medina-Echeverz J. Intratumoral virotherapy with 4-1BBL armed modified vaccinia Ankara eradicates solid tumors and promotes protective immune memory. J Immunother Cancer 2021; 9(2): e001586

[191] Ju F, Luo Y, Lin C, Jia X, Xu Z, Tian R, Lin Y, Zhao M, Chang Y, Huang X, Li S, Ren W, Qin Y, Yu M, Jia J, Han J, Luo W, Zhang J, Fu G, Ye X, Huang C, Xia N. Oncolytic virus expressing PD-1 inhibitors activates a collaborative intratumoral immune response to control tumor and synergizes with CTLA-4 or TIM-3 blockade. J Immunother Cancer 2022; 10(6): e004762

[192] Zuo S, Wei M, He B, Chen A, Wang S, Kong L, Zhang Y, Meng G, Xu T, Wu J, Yang F, Zhang H, Wang S, Guo C, Wu J, Dong J, Wei J. Enhanced antitumor efficacy of a novel oncolytic vaccinia virus encoding a fully monoclonal antibody against T-cell immunoglobulin and ITIM domain (TIGIT). EBioMedicine 2021; 64: 103240

[193] Arnone CM, Polito VA, Mastronuzzi A, Carai A, Diomedi FC, Antonucci L, Petrilli LL, Vinci M, Ferrari F, Salviato E, Scarsella M, De Stefanis C, Weber G, Quintarelli C, De Angelis B, Brenner MK, Gottschalk S, Hoyos V, Locatelli F, Caruana I, Del Bufalo F. Oncolytic adenovirus and gene therapy with EphA2-BiTE for the treatment of pediatric high-grade gliomas. J Immunother Cancer 2021; 9(5): e001930

[194] de Sostoa J, Fajardo CA, Moreno R, Ramos MD, Farrera-Sal M, Alemany R. Targeting the tumor stroma with an oncolytic adenovirus secreting a fibroblast activation protein-targeted bispecific T-cell engager. J Immunother Cancer 2019; 7(1): 19

[195] Barlabé P, Sostoa J, Fajardo CA, Alemany R, Moreno R. Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers. Cancer Gene Ther 2020; 27(5): 383–388

[196] Khalique H, Baugh R, Dyer A, Scott EM, Frost S, Larkin S, Lei-Rossmann J, Seymour LW. Oncolytic herpesvirus expressing PD-L1 BiTE for cancer therapy: exploiting tumor immune suppression as an opportunity for targeted immunotherapy. J Immunother Cancer 2021; 9(4): e001292

[197] Lei W, Ye Q, Hao Y, Chen J, Huang Y, Yang L, Wang S, Qian W. CD19-targeted BiTE expression by an oncolytic vaccinia virus significantly augments therapeutic efficacy against B-cell lymphoma. Blood Cancer J 2022; 12(2): 35

[198] Yu F, Wang X, Guo ZS, Bartlett DL, Gottschalk SM, Song XT. T-cell engager-armed oncolytic vaccinia virus significantly enhances antitumor therapy. Mol Ther 2014; 22(1): 102–111

[199] Cohn DE, Sill MW, Walker JL, O’Malley D, Nagel CI, Rutledge TL, Bradley W, Richardson DL, Moxley KM, Aghajanian C. Randomized phase IIB evaluation of weekly paclitaxel versus weekly paclitaxel with oncolytic reovirus (Reolysin®) in recurrent ovarian, tubal, or peritoneal cancer: an NRG oncology/gynecologic oncology group study. Gynecol Oncol 2017; 146(3): 477–483

[200] Galanis E, Hartmann LC, Cliby WA, Long HJ, Peethambaram PP, Barrette BA, Kaur JS, Haluska PJ Jr, Aderca I, Zollman PJ, Sloan JA, Keeney G, Atherton PJ, Podratz KC, Dowdy SC, Stanhope CR, Wilson TO, Federspiel MJ, Peng KW, Russell SJ. Phase I trial of intraperitoneal administration of an oncolytic measles virus strain engineered to express carcinoembryonic antigen for recurrent ovarian cancer. Cancer Res 2010; 70(3): 875–882

[201] McGray AJR, Huang RY, Battaglia S, Eppolito C, Miliotto A, Stephenson KB, Lugade AA, Webster G, Lichty BD, Seshadri M, Kozbor D, Odunsi K. Oncolytic Maraba virus armed with tumor antigen boosts vaccine priming and reveals diverse therapeutic response patterns when combined with checkpoint blockade in ovarian cancer. J Immunother Cancer 2019; 7(1): 189

[202] Chesney JA, Puzanov I, Collichio FA, Singh P, Milhem MM, Glaspy J, Hamid O, Ross M, Friedlander P, Garbe C, Logan T, Hauschild A, Lebbé C, Joshi H, Snyder W, Mehnert JM. Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase II trial. J Immunother Cancer 2023; 11(5): e006270

[203] Vähä-Koskela M, Hinkkanen A. Tumor restrictions to oncolytic virus. Biomedicines 2014; 2(2): 163–194

[204] El-Sayes N, Vito A, Mossman K. Tumor heterogeneity: a great barrier in the age of cancer immunotherapy. cancers (Basel) 2021; 13(4): 806

[205] Suzuki T, Uchida H, Shibata T, Sasaki Y, Ikeda H, Hamada-Uematsu M, Hamasaki R, Okuda K, Yanagi S, Tahara H. Potent anti-tumor effects of receptor-retargeted syncytial oncolytic herpes simplex virus. Mol Ther Oncolytics 2021; 22: 265–276

[206] van Erp EA, Kaliberova LN, Kaliberov SA, Curiel DT. Retargeted oncolytic adenovirus displaying a single variable domain of camelid heavy-chain-only antibody in a fiber protein. Mol Ther Oncolytics 2015; 2: 15001

[207] Evgin L, Kottke T, Tonne J, Thompson J, Huff AL, van Vloten J, Moore M, Michael J, Driscoll C, Pulido J, Swanson E, Kennedy R, Coffey M, Loghmani H, Sanchez-Perez L, Olivier G, Harrington K, Pandha H, Melcher A, Diaz RM, Vile RG. Oncolytic virus-mediated expansion of dual-specific CAR T cells improves efficacy against solid tumors in mice. Sci Transl Med 2022; 14(640): eabn2231

[208] Rezaei R, Esmaeili Gouvarchin Ghaleh H, Farzanehpour M, Dorostkar R, Ranjbar R, Bolandian M, Mirzaei Nodooshan M, Ghorbani Alvanegh A. Combination therapy with CAR T cells and oncolytic viruses: a new era in cancer immunotherapy. Cancer Gene Ther 2022; 29(6): 647–660

[209] Schirrmacher V. Cancer vaccines and oncolytic viruses exert profoundly lower side effects in cancer patients than other systemic therapies: a comparative analysis. Biomedicines 2020; 8(3): 61

[210] Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, Olszanski AJ, Malvehy J, Cebon J, Fernandez E, Kirkwood JM, Gajewski TF, Chen L, Gorski KS, Anderson AA, Diede SJ, Lassman ME, Gansert J, Hodi FS, Long GV. Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy. Cell 2018; 174(4): 1031–1032

[211] Liu W, Liu Y, Hu C, Xu C, Chen J, Chen Y, Cai J, Yan G, Zhu W. Cytotoxic T lymphocyte-associated protein 4 antibody aggrandizes antitumor immune response of oncolytic virus M1 via targeting regulatory T cells. Int J Cancer 2021; 149(6): 1369–1384

[212] Zhang B, Cheng P. Improving antitumor efficacy via combinatorial regimens of oncolytic virotherapy. Mol Cancer 2020; 19(1): 158

[213] Zhu Z, McGray AJR, Jiang W, Lu B, Kalinski P, Guo ZS. Improving cancer immunotherapy by rationally combining oncolytic virus with modulators targeting key signaling pathways. Mol Cancer 2022; 21(1): 196

RIGHTS & PERMISSIONS

Higher Education Press