Tumor-derived exosomes: immune properties and clinical application in lung cancer

Jing Wu , Suyao Li , Pengfei Zhang

Cancer Drug Resistance ›› 2022, Vol. 5 ›› Issue (1) : 102 -13.

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Cancer Drug Resistance ›› 2022, Vol. 5 ›› Issue (1) :102 -13. DOI: 10.20517/cdr.2021.99
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Tumor-derived exosomes: immune properties and clinical application in lung cancer

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Abstract

Lung cancer is the leading cause of cancer-related death worldwide. Despite advances in diagnosis and treatment of lung cancer, the overall survival remains poor. Evidence indicates that lung cancer development is a complex and dynamic process that involves interactions between tumor cells and their microenvironments, including immune cells. Exosomes are small extracellular vesicles secreted by most cell types; they contain functional molecules that allow intercellular communication. Tumor-derived exosomes (TEXs) carry both immunosuppressive and immunostimulatory mediators and may be involved in various immunomodulatory effects. TEXs, which partially mimic profiles of the parent cells, are a potential source of cancer biomarkers for prognosis, diagnosis, and prediction of response to therapy. In addition, TEXs may interfere with immunotherapies, but they also could be used as adjuvants and antigenic components in vaccines against lung cancer. In the context of lung cancer, identifying TEXs and understanding their contribution to tumorigenesis and the response to immunotherapies represents a challenging research area.

Keywords

Lung cancer / tumor-derived exosomes / cancer biomarkers / immunotherapies

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Jing Wu, Suyao Li, Pengfei Zhang. Tumor-derived exosomes: immune properties and clinical application in lung cancer. Cancer Drug Resistance, 2022, 5(1): 102-13 DOI:10.20517/cdr.2021.99

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References

[1]

Herbst RS,Boshoff C.The biology and management of non-small cell lung cancer.Nature2018;553:446-54

[2]

Gadgeel S,Speranza G.Updated analysis from KEYNOTE-189: pembrolizumab or placebo plus pemetrexed and platinum for previously untreated metastatic nonsquamous non-small-cell lung cancer.J Clin Oncol2020;38:1505-17

[3]

Mok TSK,Kudaba I.Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial.Lancet2019;393:1819-30

[4]

Cao C,Chen C,Bott M.Neoadjuvant immunotherapy for patients with non-small cell lung cancer-current evidence.Ann Transl Med2020;8:1476 PMCID:PMC7729370

[5]

Xu Z,Gong Z.Exosome-based immunotherapy: a promising approach for cancer treatment.Mol Cancer2020;19:160 PMCID:PMC7661275

[6]

Zhu L,Wang S.Isolation and characterization of exosomes for cancer research.J Hematol Oncol2020;13:152 PMCID:PMC7652679

[7]

Olejarz W,Żołnierzak A,Lorenc T.Tumor-derived exosomes in immunosuppression and immunotherapy.J Immunol Res2020;2020:6272498 PMCID:PMC7261328

[8]

Whiteside TL. Tumor-derived exosomes and their role in cancer progression. Elsevier; 2016. p. 103-41.

[9]

Soung YH,Zhang V.Exosomes in cancer diagnostics.Cancers (Basel)2017;9:8 PMCID:PMC5295779

[10]

Sharma S. Techniques associated with exosome isolation for biomarker development: liquid biopsies for ovarian cancer detection. In: Thurin M, Cesano A, Marincola FM, editors. Biomarkers for immunotherapy of cancer. New York: Springer; 2020. p. 181-99.

[11]

Sandfeld-Paulsen B,Bæk R.Exosomal proteins as prognostic biomarkers in non-small cell lung cancer.Mol Oncol2016;10:1595-602 PMCID:PMC5423137

[12]

Tian X,Li Z,Wang S.Tumor-derived exosomes, myeloid-derived suppressor cells, and tumor microenvironment.J Hematol Oncol2019;12:84 PMCID:PMC6704713

[13]

Xie F,Fang M.Extracellular vesicles in cancer immune microenvironment and cancer immunotherapy.Adv Sci (Weinh)2019;6:1901779 PMCID:PMC6918121

[14]

Salimi L,Jabbari N.Synergies in exosomes and autophagy pathways for cellular homeostasis and metastasis of tumor cells.Cell Biosci2020;10:64 PMCID:PMC7218515

[15]

Taghikhani A,Sharifzad F,Ebrahimi M.Engineered tumor-derived extracellular vesicles: potentials in cancer immunotherapy.Front Immunol2020;11:221 PMCID:PMC7069476

[16]

Gupta A.Exosomes as mediators of neuroinflammation.J Neuroinflammation2014;11:68 PMCID:PMC3994210

[17]

Czystowska-Kuzmicz M.The potential role of tumor-derived exosomes in diagnosis, prognosis, and response to therapy in cancer.Expert Opin Biol Ther2021;21:241-58 PMCID:PMC7880862

[18]

Whiteside TL.The effect of tumor-derived exosomes on immune regulation and cancer immunotherapy.Future Oncol2017;13:2583-92 PMCID:PMC5827821

[19]

Whiteside TL.The emerging role of plasma exosomes in diagnosis, prognosis and therapies of patients with cancer.Contemp Oncol (Pozn)2018;22:38-40 PMCID:PMC5885072

[20]

Chen R,Qian Z.The biological functions and clinical applications of exosomes in lung cancer.Cell Mol Life Sci2019;76:4613-33

[21]

Hu C,Lukas C,Chen J.Role of exosomal microRNAs in lung cancer biology and clinical applications.Cell Prolif2020;53:e12828 PMCID:PMC7309943

[22]

Wieckowski EU,Szajnik M,Storkus WJ.Tumor-derived microvesicles promote regulatory T cell expansion and induce apoptosis in tumor-reactive activated CD8+ T lymphocytes.J Immunol2009;183:3720-30 PMCID:PMC3721354

[23]

Chen G,Zhang W.Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response.Nature2018;560:382-6 PMCID:PMC6095740

[24]

Poggio M,Pai CC.Suppression of exosomal PD-L1 induces systemic anti-tumor immunity and memory.Cell2019;177:414-27.e13 PMCID:PMC6499401

[25]

Kim JW,Taylor DD,Watkins S.Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes.Clin Cancer Res2005;11:1010-20

[26]

Abusamra AJ,Zheng X.Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis.Blood Cells Mol Dis2005;35:169-73

[27]

Czystowska M,Szczepanski MJ.IRX-2, a novel immunotherapeutic, protects human T cells from tumor-induced cell death.Cell Death Differ2009;16:708-18 PMCID:PMC3721331

[28]

Huang SH,Zhang J,Ye S.Epidermal growth factor receptor-containing exosomes induce tumor-specific regulatory T cells.Cancer Invest2013;31:330-5

[29]

Yin Y,Chen X.Tumor-secreted miR-214 induces regulatory T cells: a major link between immune evasion and tumor growth.Cell Res2014;24:1164-80 PMCID:PMC4185347

[30]

Szajnik M,Szczepanski MJ,Whiteside TL.Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells (Treg).PLoS One2010;5:e11469 PMCID:PMC2908536

[31]

Liu B,Zhu Y.Exosome-derived microRNA-433 inhibits tumorigenesis through incremental infiltration of CD4 and CD8 cells in non-small cell lung cancer.Oncol Lett2021;22:607 PMCID:PMC8227510

[32]

Fabbri M,Calore F.MicroRNAs bind to toll-like receptors to induce prometastatic inflammatory response.Proc Natl Acad Sci U S A2012;109:E2110-6 PMCID:PMC3412003

[33]

Marcus A,Thompson TW.Recognition of tumors by the innate immune system and natural killer cells.Adv Immunol2014;122:91-128 PMCID:PMC4228931

[34]

Alipoor SD,Varahram M.The potential biomarkers and immunological effects of tumor-derived exosomes in lung cancer.Front Immunol2018;9:819 PMCID:PMC5915468

[35]

Berchem G,Bosseler M.Hypoxic tumor-derived microvesicles negatively regulate NK cell function by a mechanism involving TGF-β and miR23a transfer.Oncoimmunology2016;5:e1062968 PMCID:PMC4839360

[36]

Whiteside TL.Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour-derived exosomes).Biochem Soc Trans2013;41:245-51 PMCID:PMC3721347

[37]

Clayton A,Court J,Mason MD.Human tumor-derived exosomes down-modulate NKG2D expression.J Immunol2008;180:7249-58

[38]

Ashiru O,Fernández-Messina L.Natural killer cell cytotoxicity is suppressed by exposure to the human NKG2D ligand MICA*008 that is shed by tumor cells in exosomes.Cancer Res2010;70:481-9 PMCID:PMC2817492

[39]

Liu Y,Zhuang X.Contribution of MyD88 to the tumor exosome-mediated induction of myeloid derived suppressor cells.Am J Pathol2010;176:2490-9 PMCID:PMC2861113

[40]

Deng W,Zhang L.Antitumor immunity. A shed NKG2D ligand that promotes natural killer cell activation and tumor rejection.Science2015;348:136-9 PMCID:PMC4856222

[41]

Filipazzi P,Villa A,Huber V.Recent advances on the role of tumor exosomes in immunosuppression and disease progression.Semin Cancer Biol2012;22:342-9

[42]

Szczepanski MJ,Welsh A,Boyiadzis M.Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-beta1.Haematologica2011;96:1302-9 PMCID:PMC3166100

[43]

Kunigelis KE.The dichotomy of tumor exosomes (TEX) in cancer immunity: is it all in the ConTEXt?.Vaccines (Basel)2015;3:1019-51 PMCID:PMC4693230

[44]

Hosseini R,Yousefi H.The roles of tumor-derived exosomes in altered differentiation, maturation and function of dendritic cells.Mol Cancer2021;20:83 PMCID:PMC8170799

[45]

Ning Y,Wu Q.Tumor exosomes block dendritic cells maturation to decrease the T cell immune response.Immunol Lett2018;199:36-43

[46]

Ludwig S,Theodoraki MN.Molecular and functional profiles of exosomes from HPV(+) and HPV(-) head and neck cancer cell lines.Front Oncol2018;8:445 PMCID:PMC6194188

[47]

Xiang X,Liu C.Induction of myeloid-derived suppressor cells by tumor exosomes.Int J Cancer2009;124:2621-33 PMCID:PMC2757307

[48]

Chalmin F,Mignot G.Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells.J Clin Invest2010;120:457-71 PMCID:PMC2810085

[49]

Mignot G,Ladoire S,Ghiringhelli F.Tumor exosome-mediated MDSC activation.Am J Pathol2011;178:1403-4; author reply 1404-5 PMCID:PMC3069877

[50]

Xiang X,Zhuang X.TLR2-mediated expansion of MDSCs is dependent on the source of tumor exosomes.Am J Pathol2010;177:1606-10 PMCID:PMC2947257

[51]

Zhang X,Tang Y.miR-21a in exosomes from Lewis lung carcinoma cells accelerates tumor growth through targeting PDCD4 to enhance expansion of myeloid-derived suppressor cells.Oncogene2020;39:6354-69

[52]

Hsu YL,Chang WA.Hypoxic lung-cancer-derived extracellular vesicle microRNA-103a increases the oncogenic effects of macrophages by targeting PTEN.Mol Ther2018;26:568-81 PMCID:PMC5835028

[53]

Pritchard A,Wang Y.Lung tumor cell-derived exosomes promote M2 macrophage polarization.Cells2020;9:1303 PMCID:PMC7290460

[54]

Chen T,Li C.Tumor-derived exosomal circFARSA mediates M2 macrophage polarization via the PTEN/PI3K/AKT pathway to promote non-small cell lung cancer metastasis.Cancer Treat Res Commun2021;28:100412

[55]

Zhang L.Exosomes in cancer development, metastasis, and immunity.Biochim Biophys Acta Rev Cancer2019;1871:455-68 PMCID:PMC6542596

[56]

Whiteside TL,Hong CS.Tumor-derived exosomes (TEX) and their role in immuno-oncology.Int J Mol Sci2021;22:6234 PMCID:PMC8229953

[57]

Chaput N.Exosomes: immune properties and potential clinical implementations.Semin Immunopathol2011;33:419-40

[58]

Greening DW,Xu R,Chen W.Exosomes and their roles in immune regulation and cancer.Semin Cell Dev Biol2015;40:72-81

[59]

Gastpar R,Bausero MA.Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells.Cancer Res2005;65:5238-47 PMCID:PMC1785299

[60]

Vega VL,Frey T.Hsp70 translocates into the plasma membrane after stress and is released into the extracellular environment in a membrane-associated form that activates macrophages.J Immunol2008;180:4299-307

[61]

Li XB,Schluesener HJ.Role of exosomes in immune regulation.J Cell Mol Med2006;10:364-75 PMCID:PMC3933127

[62]

Liu J,Wang J.Tumor cell-derived exosomal miR-770 inhibits M2 macrophage polarization via targeting MAP3K1 to Inhibit the invasion of non-small cell lung cancer cells.Front Cell Dev Biol2021;9:679658 PMCID:PMC8236888

[63]

Jiang L,Du Y.Exosomes: diagnostic biomarkers and therapeutic delivery vehicles for cancer.Mol Pharm2019;16:3333-49

[64]

Nedaeinia R,Jazayeri MH.Circulating exosomes and exosomal microRNAs as biomarkers in gastrointestinal cancer.Cancer Gene Ther2017;24:48-56

[65]

Shan Z,Zhang Y.The role of tumor-derived exosomes in the abscopal effect and immunotherapy.Life (Basel)2021;11:381 PMCID:PMC8145657

[66]

Jakobsen KR,Bæk R,Sorensen BS.Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma.J Extracell Vesicles2015;4:26659 PMCID:PMC4348413

[67]

Vykoukal J,Aguilar-Bonavides C.Plasma-derived extracellular vesicle proteins as a source of biomarkers for lung adenocarcinoma.Oncotarget2017;8:95466-80 PMCID:PMC5707035

[68]

Niu L,Wang N,Song X.Tumor-derived exosomal proteins as diagnostic biomarkers in non-small cell lung cancer.Cancer Sci2019;110:433-42 PMCID:PMC6317937

[69]

Gao J,Li X.Expression profiles and clinical value of plasma exosomal Tim-3 and Galectin-9 in non-small cell lung cancer.Biochem Biophys Res Commun2018;498:409-15

[70]

Li Y,Qiu F.Proteomic identification of exosomal LRG1: a potential urinary biomarker for detecting NSCLC.Electrophoresis2011;32:1976-83

[71]

Rabinowits G,Day JM,Kloecker GH.Exosomal microRNA: a diagnostic marker for lung cancer.Clin Lung Cancer2009;10:42-6

[72]

Jin X,Chen H.Evaluation of tumor-derived exosomal miRNA as potential diagnostic biomarkers for early-stage non-small cell lung cancer using next-generation sequencing.Clin Cancer Res2017;23:5311-9

[73]

Xia J,Dai L,Wang L.Serum exosomal microRNAs as predictive markers for EGFR mutations in non-small-cell lung cancer.J Clin Lab Anal2021;35:e23743 PMCID:PMC8128312

[74]

Zhang ZJ,Xie L.Circulating serum exosomal miR-20b-5p and miR-3187-5p as efficient diagnostic biomarkers for early-stage non-small cell lung cancer.Exp Biol Med (Maywood)2020;245:1428-36 PMCID:PMC7553089

[75]

Grimolizzi F,Leoni F.Exosomal miR-126 as a circulating biomarker in non-small-cell lung cancer regulating cancer progression.Sci Rep2017;7:15277 PMCID:PMC5681649

[76]

Tamiya H,Saito A.Exosomal MicroRNA expression profiling in patients with lung adenocarcinoma-associated malignant pleural effusion.Anticancer Res2018;38:6707-14

[77]

Hydbring P,Zhang Y.Exosomal RNA-profiling of pleural effusions identifies adenocarcinoma patients through elevated miR-200 and LCN2 expression.Lung Cancer2018;124:45-52

[78]

Dejima H,Kanaoka R,Kawamura M.Exosomal microRNA in plasma as a non-invasive biomarker for the recurrence of non-small cell lung cancer.Oncol Lett2017;13:1256-63 PMCID:PMC5403401

[79]

Zhang L,Zhai R.Downregulation of exosomal let-7a-5p in dust exposed- workers contributes to lung cancer development.Respir Res2018;19:235 PMCID:PMC6267915

[80]

Luo R,Chen J.Reduced circulating exosomal miR-382 predicts unfavorable outcome in non-small cell lung cancer.Int J Clin Exp Pathol2021;14:469-74 PMCID:PMC8085833

[81]

Zhang R,Wang Z.Serum long non coding RNA MALAT-1 protected by exosomes is up-regulated and promotes cell proliferation and migration in non-small cell lung cancer.Biochem Biophys Res Commun2017;490:406-14

[82]

Dong Q,Liu S,Zhang M.Tumor-derived exosomal eIF4E as a biomarker for survival prediction in patients with non-small cell lung cancer.Med Sci Monit2020;26:e923210 PMCID:PMC7297025

[83]

Xu X,Sun L.Exosome-transferred hsa_circ_0014235 promotes DDP chemoresistance and deteriorates the development of non-small cell lung cancer by mediating the miR-520a-5p/CDK4 pathway.Cancer Cell Int2020;20:552 PMCID:PMC7672955

[84]

Song Z,Ma P.Exosomal miR-4443 promotes cisplatin resistance in non-small cell lung carcinoma by regulating FSP1 m6A modification-mediated ferroptosis.Life Sci2021;276:119399

[85]

Li M,Hua Y.Exosomal miR-92b-3p promotes chemoresistance of small cell lung cancer through the PTEN/AKT pathway.Front Cell Dev Biol2021;9:661602 PMCID:PMC8201786

[86]

Dinh TK,Chałubińska-Fendler J.Circulating miR-29a and miR-150 correlate with delivered dose during thoracic radiation therapy for non-small cell lung cancer.Radiat Oncol2016;11:61 PMCID:PMC4847218

[87]

Janpipatkul K,Watcharenwong P.Exosomal microRNAs as potential biomarkers for osimertinib resistance of non-small cell lung cancer patients.Cancer Biomark2021;31:281-94

[88]

Hisakane K,Sugano T.Exosome-derived miR-210 involved in resistance to osimertinib and epithelial-mesenchymal transition in EGFR mutant non-small cell lung cancer cells.Thorac Cancer2021;12:1690-8 PMCID:PMC8169289

[89]

Yang B,Chang L.Tumor-derived exosomal circRNA_102481 contributes to EGFR-TKIs resistance via the miR-30a-5p/ROR1 axis in non-small cell lung cancer.Aging (Albany NY)2021;13:13264-86 PMCID:PMC8148492

[90]

Peng XX,Wu X.Correlation of plasma exosomal microRNAs with the efficacy of immunotherapy in EGFR/ALK wild-type advanced non-small cell lung cancer.J Immunother Cancer2020;8:e000376

[91]

Battke C,Welsch U.Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC.Cancer Immunol Immunother2011;60:639-48

[92]

Meehan K.The contribution of tumour-derived exosomes to the hallmarks of cancer.Crit Rev Clin Lab Sci2016;53:121-31

[93]

Kim DH,Choi YJ.Exosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer.Exp Mol Med2019;51:1-13 PMCID:PMC6802663

[94]

Pitt JM,Viaud S.Dendritic cell-derived exosomes as immunotherapies in the fight against cancer.J Immunol2014;193:1006-11

[95]

Batrakova EV.Using exosomes, naturally-equipped nanocarriers, for drug delivery.J Control Release2015;219:396-405 PMCID:PMC4656109

[96]

van der Pol E, Böing AN, Harrison P, Sturk A, Nieuwland R. Classification, functions, and clinical relevance of extracellular vesicles.Pharmacol Rev2012;64:676-705

[97]

Wang J,Lin Z,Chen M.More efficient induction of antitumor T cell immunity by exosomes from CD40L gene-modified lung tumor cells.Mol Med Rep2014;9:125-31

[98]

Li W,Tian F.Exosomes derived from Rab27aoverexpressing tumor cells elicit efficient induction of antitumor immunity.Mol Med Rep2013;8:1876-82

[99]

Raposo G,Stoorvogel W.B lymphocytes secrete antigen-presenting vesicles.J Exp Med1996;183:1161-72 PMCID:PMC2192324

[100]

Zitvogel L,Lozier A.Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes.Nat Med1998;4:594-600

[101]

Lee EY,Yoon YJ.Therapeutic effects of autologous tumor-derived nanovesicles on melanoma growth and metastasis.PLoS One2012;7:e33330 PMCID:PMC3305328

[102]

Marton A,Kusz E.Melanoma cell-derived exosomes alter macrophage and dendritic cell functions in vitro.Immunol Lett2012;148:34-8

[103]

Gu X,Büchler MW.Improved vaccine efficacy of tumor exosome compared to tumor lysate loaded dendritic cells in mice.Int J Cancer2015;136:E74-84

[104]

Wang C,Wu Y,Li F.Tumor cell-associated exosomes robustly elicit anti-tumor immune responses through modulating dendritic cell vaccines in lung tumor.Int J Biol Sci2020;16:633-43 PMCID:PMC6990923

[105]

Liu H,Peng Y.Dendritic cells loaded with tumor derived exosomes for cancer immunotherapy.Oncotarget2018;9:2887-94 PMCID:PMC5788689

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