HDAC inhibitors overcome immunotherapy resistance in B-cell lymphoma
Received date: 03 Dec 2019
Accepted date: 30 Jan 2020
Published date: 15 Jul 2020
Copyright
Immunotherapy has been applied successfully to treat B-cell lymphomas in preclinical models or clinical settings. However, immunotherapy resistance is a major challenge for B-cell lymphoma treatment. To overcome this issue, combinatorial therapeutic strategies have been pursued to achieve a better efficacy for treating B-cell lymphomas. One of such strategies is to combine immunotherapy with histone deacetylase (HDAC) inhibitors. HDAC inhibitors can potentially increase tumor immunogenicity, promote anti-tumor immune responses, or reverse immunosuppressive tumor environments. Thus, the combination of HDAC inhibitors and immunotherapy has drawn much attention in current cancer treatment. However, not all HDAC inhibitors are created equal and their net effects are highly dependent on the specific inhibitors used and the HDACs they target. Hence, we suggest that optimal treatment efficacy requires personalized design and rational combination based on prognostic biomarkers and unique profiles of HDAC inhibitors. Here, we discuss the possible mechanisms by which B-cell lymphomas acquire immunotherapy resistance and the effects of HDAC inhibitors on tumor cells and immune cells that could help overcome immunotherapy resistance.
Xiaoguang Wang , Brittany C. Waschke , Rachel A Woolaver , Samantha M. Y. Chen , Zhangguo Chen , Jing H. Wang . HDAC inhibitors overcome immunotherapy resistance in B-cell lymphoma[J]. Protein & Cell, . DOI: 10.1007/s13238-020-00694-x
1 |
Akimova T,Ge G, Golovina T, Mikheeva T, Wang L, Riley JL, Hancock WW (2010) Histone/protein deacetylase inhibitors increase suppressive functions of human FOXP3+ Tregs. Clin Immunol 136:348–363
|
2 |
Assouline SE, Nielsen TH, Yu S, Alcaide M, Chong L, MacDonald D, Tosikyan A, Kukreti V, Kezouh A,Petrogiannis-Haliotis T
|
3 |
Azzaoui I, Uhel F, Rossille D, Pangault C, Dulong J, Le Priol J, Lamy T, Houot R, Le Gouill S, Cartron G
|
4 |
Beier UH, Wang L, Bhatti TR, Liu Y, Han R, Ge G, Hancock WW (2011) Sirtuin-1 targeting promotes Foxp3+ T-regulatory cell function and prolongs allograft survival. Mol Cell Biol 31:1022–1029
|
5 |
Betsch A, Rutgeerts O, Fevery S, Sprangers B, Verhoef G,Dierickx D, Beckers M (2018) Myeloid-derived suppressor cells in lymphoma: the good, the bad and the ugly. Blood Rev 32:490–498
|
6 |
Bobrowicz M, Dwojak M, Pyrzynska B, Stachura J, Muchowicz A, Berthel E, Dalla-Venezia N, Kozikowski M, Siernicka M, Miazek N
|
7 |
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA-A Cancer Journal for Clinicians 68:394–424
|
8 |
Cao K,Wang G, Li W, Zhang L, Wang R, Huang Y, Du L, Jiang J, Wu C, He X
|
9 |
Carey CD, Gusenleitner D, Lipschitz M, Roemer MGM, Stack EC, Gjini E,Hu X, Redd R, Freeman GJ, Neuberg D
|
10 |
Challa-Malladi M, Lieu YK, Califano O, Holmes AB, Bhagat G, Murty VV, Dominguez-Sola D, Pasqualucci L, Dalla-Favera R(2011) Combined genetic inactivation of beta 2-Microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer Cell 20:728–740
|
11 |
Chau CH, Steeg PS, Figg WD (2019) Antibody-drug conjugates for cancer. Lancet 394:793–804
|
12 |
Chen R, Frankel P, Popplewell L, Siddiqi T, Ruel N, Rotter A, Thomas SH, Mott M,Nathwani N, Htut M
|
13 |
Chen Z, Elos MT, Viboolsittiseri SS, Gowan K, Leach SM, Rice M, Eder MD, Jones K, Wang JH (2016) Combined deletion of Xrcc4 and Trp53 in mouse germinal center B cells leads to novel B cell lymphomas with clonal heterogeneity. J Hematol Oncol 9:2
|
14 |
Chen Z, Wang JH (2014) Generation and repair of AID-initiated DNA lesions in B lymphocytes. Front Med 8:201–216
|
15 |
Cheng J, Zhao L, Zhang Y, Qin Y, Guan Y, Zhang T,Liu C, Zhou J(2019) Understanding the mechanisms of resistance to CAR T-cell therapy in malignancies. Front Oncol 9:1237
|
16 |
Chu Y, Yahr A, Ayello J, Cairo MS (2015) Effectively targeting Burkitt lymphoma by anti-CD20 chimeric antigen receptor (CAR) modified expanded natural killer cells combined with a histone deacetylase inhibitor, romidepsin in vitro and in humanized NSG mice. Biol Blood Marrow Transplant 21:S152–S153
|
17 |
Chu Y, Yahr A, Huang B,Ayello J, Barth MS, Cairo M (2017) Romidepsin alone or in combination with anti-CD20 chimeric antigen receptor expanded natural killer cells targeting Burkitt lymphoma in vitro and in immunodeficient mice. Oncoimmunology 6:e1341031
|
18 |
Cycon KA, Mulvaney K, Rimsza LM, Persky D, Murphy SP (2013) Histone deacetylase inhibitors activate CIITA and MHC class II antigen expression in diffuse large B-cell lymphoma. Immunology 140:259–272
|
19 |
de Charette M, Houot R (2018) Hide or defend, the two strategies of lymphoma immune evasion: potential implications for immunotherapy. Haematologica 103:1256–1268
|
20 |
de Charette M, Marabelle A, Houot R (2016) Turning tumour cells into antigen presenting cells: The next step to improve cancer immunotherapy? Eur J Cancer 68:134–147
|
21 |
de Zoeten EF, Wang L, Butler K, Beier UH, Akimova T, Sai H, Bradner JE, Mazitschek R, Kozikowski AP, Matthias P
|
22 |
Deng S, Hu Q, Zhang H, Yang F, Peng C, Huang C (2019) HDAC3 inhibition upregulates PD-L1 expression in B-cell lymphomas and augments the efficacy of anti-PD-L1 therapy. Mol Cancer Ther 18:900–908
|
23 |
Dias JN, Aguiar SI, Pereira DM, André AS, Gano L, Correia JD, Carrapiço B, Rçtgen B, Malhç R, Peleteiro C (2018) The histone deacetylase inhibitor panobinostat is a potent antitumor agent in canine diffuse large B-cell lymphoma. Oncotarget 9:28586
|
24 |
Diepstra A, Van Imhoff GW, Karim-Kos HE, Van den Berg A,Meerman GJT, Niens M,Nolte IM, Bastiaannet E, Schaapveld M, Vellenga E
|
25 |
Diepstra A, van Imhoff GW, Karim-Kos HE, van den Berg A, te Meerman GJ, Niens M, Nolte IM, Bastiaannet E,Schaapveld M, Vellenga E
|
26 |
Fangazio M,Dominguez-Sola D, Tabbo F, Rossi D, Teruya-Feldstein J,Boldorini R, Gaidano G,Bhagat G, Inghirami G, Pasqualucci L
|
27 |
Frys S, Simons Z,Hu Q, Barth MJ, Gu JJ, Mavis C, Skitzki J, Song L, Czuczman MS, Hernandez-Ilizaliturri FJ (2015) Entinostat, a novel histone deacetylase inhibitor is active in B-cell lymphoma and enhances the anti-tumour activity of rituximab and chemotherapy agents. Br J Haematol 169:506–519
|
28 |
Garrido F, Aptsiauri N, Doorduijn EM, Lora AMG, van Hall T (2016) The urgent need to recover MHC class I in cancers for effective immunotherapy. Curr Opin Immunol 39:44–51
|
29 |
Garrido F,Cabrera T, Aptsiauri N (2010) “Hard” and “soft” lesions underlying the HLA Class I alterations in cancer cells: implications for immunotherapy. Int J Cancer 127:249–256
|
30 |
Gil VS, Bhagat G, Howell L, Zhang J,Kim CH, Stengel S, Vega F, Zelent A, Petrie K (2016) Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice. Dis Model Mech 9:1483–1495
|
31 |
Grunewald CM, Schulz WA, Skowron MA, Hoffmann MJ, Niegisch G (2018) Tumor immunotherapy-the potential of epigenetic drugs to overcome resistance. Transl Cancer Res 7:1151–1160
|
32 |
Gryder BE, Sodji QH, Oyelere AK (2012) Targeted cancer therapy: giving histone deacetylase inhibitors all they need to succeed. Future Med Chem 4:505–524
|
33 |
Hiraga J,Tomita A, Sugimoto T, Shimada K, Ito M, Nakamura S, Kiyoi H, Kinoshita T, Naoe T (2009) Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: its prevalence and clinical significance. Blood 113:4885–4893
|
34 |
Huang HL, Peng CY, Lai MJ, Chen CH, Lee HY, Wang JC, Liou JP, Pan SL, Teng CM (2015) Novel oral histone deacetylase inhibitor, MPT0E028, displays potent growth-inhibitory activity against human B-cell lymphoma in vitro and in vivo. Oncotarget 6:4976–4991
|
35 |
Huang RH, Zhang XW, Min ZJ, Shadia AS, Yang SE, Liu XJ (2018) MGCD0103 induces apoptosis and simultaneously increases the expression of NF-kappa B and PD-L1 in classical Hodgkin’s lymphoma. Exp Ther Med 16:3827–3834
|
36 |
Insinga A, Monestiroli S,Ronzoni S,Gelmetti V, Marchesi F,Viale A, Altucci L, Nervi C, Minucci S, Pelicci PG (2005) Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway. Nat Med 11:71–76
|
37 |
Jiang Y, Ortega-Molina A, Geng H, Ying HY, Hatzi K, Parsa S, McNally D, Wang L, Doane AS, Agirre X
|
38 |
Johnson NA, Boyle M, Bashashati A, Leach S, Brooks-Wilson A, Sehn LH, Chhanabhai M, Brinkman RR, Connors JM, Weng AP
|
39 |
Khodadoust MS, Olsson N, Chen B, Sworder B, Shree T, Liu CL, Zhang L, Czerwinski DK, Davis MM, Levy R
|
40 |
Khodadoust MS, Olsson N,Wagar LE, Haabeth OA, Chen B, Swaminathan K, Rawson K, Liu CL, Steiner D, Lund P
|
41 |
Kim K,Skora AD, Li Z, Liu Q, Tam AJ, Blosser RL, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B
|
42 |
Klein JM, Henke A, Sauer M, Bessler M, Reiners KS, Engert A, Hansen HP, von Strandmann EP (2013) The histone deacetylase inhibitor LBH589 (panobinostat) modulates the crosstalk of lymphocytes with Hodgkin lymphoma cell lines. PLoS ONE 8: e79502
|
43 |
Kroesen M, Gielen P, Brok IC, Armandari I, Hoogerbrugge PM, Adema GJ (2014) HDAC inhibitors and immunotherapy; a double edged sword? Oncotarget 5:6558–6572
|
44 |
Kuppers R (2005) Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer 5:251–262
|
45 |
Lee SH, Yoo C, Im S, Jung JH, Choi HJ, Yoo J (2014) Expression of histone deacetylases in diffuse large B-cell lymphoma and its clinical significance. Int J Med Sci 11:994–1000
|
46 |
Liu X,Phillips AJ, Ungermannova D, Nasveschuk CG, Zhang G (2013). Macrocyclic compounds useful as inhibitors of histone deacetylases. US Patent 20130203681A1 (US Patent 20130203681A1.)
|
47 |
Lucas DM, Davis ME, Parthun MR, Mone AP, Kitada S, Cunningham KD, Flax EL, Wickham J, Reed JC, Byrd JC
|
48 |
Maloney DG (2012) Anti-CD20 antibody therapy for B-cell lymphomas. N Engl J Med 367:878–878
|
49 |
McCaw TR, Randall TD, Forero A, Buchsbaum DJ (2017) Modulation of antitumor immunity with histone deacetylase inhibitors. Immunotherapy 9:1359–1372
|
50 |
Merryman RW, Armand P,Wright KT, Rodig SJ (2017) Checkpoint blockade in Hodgkin and non-Hodgkin lymphoma. Blood Adv 1:2643–2654
|
51 |
Moreira JM, Scheipers P, Sorensen P (2003) The histone deacetylase inhibitor Trichostatin A modulates CD4+ T cell responses. BMC Cancer 3:30
|
52 |
Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T (2000) Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102:553–563
|
53 |
Murphy K, Weaver C (2017) Janeway’s immunobiology, 9th edn. Garland Science, New York,pp 1–904
|
54 |
Nakata S,Yoshida T, Horinaka M, Shiraishi T, Wakada M, Sakai T (2004) Histone deacetylase inhibitors upregulate death receptor 5/TRAIL-R2 and sensitize apoptosis induced by TRAIL/APO2-L in human malignant tumor cells. Oncogene 23:6261–6271
|
55 |
Nijland M, Veenstra RN, Visser L, Xu CH, Kushekhar K, van Imhoff GW, Kluin PM, van den Berg A, Diepstra A (2017) HLA dependent immune escape mechanisms in B-cell lymphomas: Implications for immune checkpoint inhibitor therapy? Oncoimmunology 6:e1295202
|
56 |
Ok CY, Young KH (2017) Targeting the programmed death-1 pathway in lymphoid neoplasms. Cancer Treat Rev 54:99–109
|
57 |
Olejniczak SH, Stewart CC, Donohue K, Czuczman MS (2006) A quantitative exploration of surface antigen expression in common B-cell malignancies using flow cytometry. Immunol Invest 35:93–114
|
58 |
Park JH, Riviere I, Gonen M, Wang X, Senechal B, Curran KJ, Sauter C, Wang Y, Santomasso B, Mead E
|
59 |
Perez-Duran P, de Yebenes VG, Ramiro AR (2007) Oncogenic events triggered by AID, the adverse effect of antibody diversification. Carcinogenesis 28:2427–2433
|
60 |
Rimsza LM, Farinha P,Fuchs DA, Masoudi H, Connors JM, Gascoyne RD (2007) HLA-DR protein status predicts survival in patients with diffuse large B-cell lymphoma treated on the MACOP-B chemotherapy regimen. Leukemia Lymphoma 48:542–546
|
61 |
Rimsza LM, LeBlanc ML, Unger JM, Miller TP, Grogan TM, Persky DO, Martel RR, Sabalos CM, Seligmann B, Braziel RM
|
62 |
Rimsza LM, Roberts RA, Miller TP, Unger JM, LeBlanc M, Braziel RM, Weisenberger DD, Chan WC, Muller-Hermelink HK, Jaffe ES
|
63 |
Roberts RA, Wright G, Rosenwald AR, Jaramillo MA, Grogan TM, Miller TP, Frutiger Y, Chan WC, Gascoyne RD, Ott G
|
64 |
Roemer MGM, Advani RH, Redd RA, Pinkus GS, Natkunam Y, Ligon AH, Connelly CF, Pak CJ, Carey CD, Daadi SE
|
65 |
Ropero S, Esteller M(2007) The role of histone deacetylases (HDACs) in human cancer. Mol Oncol 1:19–25
|
66 |
Rosborough BR, Castellaneta A, Natarajan S, Thomson AW, Turnquist HR (2012) Histone deacetylase inhibition facilitates GM-CSF-mediated expansion of myeloid-derived suppressor cells in vitro and in vivo. J Leukoc Biol 91:701–709
|
67 |
Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, Gascoyne RD, Muller-Hermelink HK, Smeland EB, Staudt LM
|
68 |
Roussel M, Irish JM, Menard C, Lhomme F,Tarte K, Fest T (2017) Regulatory myeloid cells: an underexplored continent in B-cell lymphomas. Cancer Immunol Immunother 66:1103–1111
|
69 |
Sahakian E, Powers JJ, Chen J,Deng SL, Cheng F, Distler A, Woods DM, Rock-Klotz J, Sodre AL, Youn JI
|
70 |
Scott DW, Gascoyne RD (2014) The tumour microenvironment in B cell lymphomas. Nat Rev Cancer 14:517–534
|
71 |
Serafini P, Mgebroff S, Noonan K, Borrello I (2008) Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res 68:5439–5449
|
72 |
Sermer D,Pasqualucci L, Wendel HG, Melnick A, Younes A (2019) Emerging epigenetic-modulating therapies in lymphoma. Nat Rev Clin Oncol 16:494–507
|
73 |
Shah NN, Maatman T, Hari P, Johnson B (2019) Multi Targeted CART Cell Therapies for B-Cell Malignancies. Front Oncol 9:146
|
74 |
Shalabi H, Kraft IL, Wang HW, Yuan CM, Yates B, Delbrook C, Zimbelman JD, Giller R, Stetler-Stevenson M, Jaffe ES
|
75 |
Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A (2017) Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 168:707–723
|
76 |
Shimizu R, Kikuchi J, Wada T, Ozawa K, Kano Y,Furukawa Y (2010) HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20 expression on lymphoma cells. Leukemia 24:1760–1768
|
77 |
Smahel M (2017) PD-1/PD-L1 blockade therapy for tumors with downregulated MHC class I expression. Int J Mol Sci 18:1331
|
78 |
Tang HD, Liang Y, Anders RA, Taube JM, Qiu XY, Mulgaonkar A, Liu X, Harrington SM, Guo JY, Xin YC
|
79 |
Tao R, de Zoeten EF, Ozkaynak E, Chen C, Wang L, Porrett PM, Li B, Turka LA, Olson EN, Greene MI
|
80 |
Taori K, Paul VJ, Luesch H (2008) Structure and activity of largazole, a potent antiproliferative agent from the Floridian marine cyanobacterium Symploca sp. J Am Chem Soc 130:1806–1807
|
81 |
Thurn KT, Thomas S, Moore A, Munster PN (2011) Rational therapeutic combinations with histone deacetylase inhibitors for the treatment of cancer. Future Oncol 7:263–283
|
82 |
Tiper IV, Webb TJ (2016) Histone deacetylase inhibitors enhance CD1d-dependent NKT cell responses to lymphoma. Cancer Immunol Immunother 65:1411–1421
|
83 |
Torres-Collad AX, Jazirehi AR (2018) Overcoming resistance of human non-Hodgkin’s lymphoma to CD19-CAR CTL therapy by celecoxib and histone deacetylase inhibitors. Cancers 10:200
|
84 |
Tsai PC, Hernandez-Ilizaliturri FJ, Bangia N, Olejniczak SH, Czuczman MS (2012) Regulation of CD20 in rituximab-resistant cell lines and B-cell non-Hodgkin lymphoma. Clin Cancer Res 18:1039–1050
|
85 |
Wang JH (2013) The role of activation-induced deaminase in antibody diversification and genomic instability. Immunol Res 55:287–297
|
86 |
Wang JH, Alt FW, Gostissa M, Datta A, Murphy M, Alimzhanov MB, Coakley KM, Rajewsky K, Manis JP, Yan CT (2008) Oncogenic transformation in the absence of Xrcc4 targets peripheral B cells that have undergone editing and switching. J Exp Med 205:3079–3090
|
87 |
Wang JH, Gostissa M, Yan CT, Goff P, Hickernell T, Hansen E, Difilippantonio S, Wesemann DR, Zarrin AA, Rajewsky K
|
88 |
Wang XG, Waschke BC, Woolaver RA, Chen ZG, Zhang G,Piscopio AD, Liu XD, Wang JH (2019) Histone deacetylase inhibition sensitizes PD1 blockade-resistant B-cell lymphomas. Cancer Immunol Res 7:1318–1331
|
89 |
West AC, Mattarollo SR, Shortt J, Cluse LA, Christiansen AJ, Smyth MJ, Johnstone RW (2013) An intact immune system is required for the anticancer activities of histone deacetylase inhibitors. Cancer Res 73:7265–7276
|
90 |
Woods DM, Sodre AL, Sarnaik A, Sotomayor EM, Weber J (2015) Class I HDAC inhibition upregulates PD-1 ligands in melanoma and increases the efficacy of PD-1 blockade. Cancer Res 3:1375–1385
|
91 |
Xiao H, Jiao J, Wang L, O’Brien S, Newick K, Wang LC, Falkensammer E, Liu Y, Han R, Kapoor V
|
92 |
Xu-Monette ZY, Zhou J, Young KH (2018) PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood 131:68–83
|
93 |
Yi M, Qin S, Zhao W, Yu S, Chu Q, Wu K (2018) The role of neoantigen in immune checkpoint blockade therapy. Exp Hematol Oncol 7:28
|
94 |
Ying Y, Taori K, Kim H, Hong J, Luesch H (2008) Total synthesis and molecular target of largazole, a histone deacetylase inhibitor. J Am Chem Soc 130:8455–8459
|
95 |
Yoon S, Eom GH (2016) HDAC and HDAC inhibitor: from cancer to cardiovascular diseases. Chonnam Med J 52:1–11
|
96 |
Youn JI, Kumar V, Collazo M, Nefedova Y,Condamine T, Cheng P, Villagra A, Antonia S, McCaffrey JC, Fishman M
|
97 |
Zain J, O’Connor OA (2010) Targeting histone deacetyalses in the treatment of B- and T-cell malignancies. Invest New Drugs 28 (Suppl 1):S58–S78
|
98 |
Zhou H, Luo YL, Zhu S, Wang X,Zhao YN, Ou XJ, Zhang T, Ma XL (2018) The efficacy and safety of anti-CD19/CD20 chimeric antigen receptor- T cells immunotherapy in relapsed or refractory B-cell malignancies: a meta-analysis. BMC Cancer 18:929
|
/
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