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Published in: Cancer Immunology, Immunotherapy 11/2020

01-11-2020 | Solid Tumor | Review

Augmenting engineered T-cell strategies in solid cancers through epigenetic priming

Authors: Aaraby Y. Nielsen, Maria Ormhøj, Sofie Traynor, Morten F. Gjerstorff

Published in: Cancer Immunology, Immunotherapy | Issue 11/2020

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Abstract

T-cell receptor (TCR)- and chimeric antigen receptor (CAR)-based adoptive cell transfer (ACT) has shown promising results in hematological malignancies, but remains immature in solid cancers. The challenges associated with identification of tumor-specific targets, the heterogenic antigen expression, limited T-cell trafficking to tumor sites and the hostile tumor microenvironment (TME), are all factors contributing to the limited efficacy of ACT therapies against solid tumors. Epigenetic priming of tumor cells and the microenvironment may be a way of overcoming these obstacles and improving the clinical efficacy of adoptive T-cell therapies in the future. Here, we review the current literature and suggest combining epigenetic modulators and ACT strategies as a way of augmenting the efficacy of TCR- and CAR-engineered T cells against solid tumors.
Literature
1.
go back to reference Zheng PP, Kros JM, Li J (2018) Approved CAR T cell therapies: ice bucket challenges on glaring safety risks and long-term impacts. Drug Discov Today 23(6):1175–1182PubMed Zheng PP, Kros JM, Li J (2018) Approved CAR T cell therapies: ice bucket challenges on glaring safety risks and long-term impacts. Drug Discov Today 23(6):1175–1182PubMed
2.
go back to reference Matsuda T, Leisegang M, Park JH, Ren L, Kato T, Ikeda Y et al (2018) Induction of neoantigen-specific cytotoxic T cells and construction of T-cell receptor-engineered T cells for ovarian cancer. Clin Cancer Res 24(21):5357–5367PubMed Matsuda T, Leisegang M, Park JH, Ren L, Kato T, Ikeda Y et al (2018) Induction of neoantigen-specific cytotoxic T cells and construction of T-cell receptor-engineered T cells for ovarian cancer. Clin Cancer Res 24(21):5357–5367PubMed
3.
go back to reference Guedan S, Calderon H, Posey AD Jr, Maus MV (2019) Engineering and Design of Chimeric Antigen Receptors. Mol Ther Methods Clin Dev 12:145–156PubMed Guedan S, Calderon H, Posey AD Jr, Maus MV (2019) Engineering and Design of Chimeric Antigen Receptors. Mol Ther Methods Clin Dev 12:145–156PubMed
4.
go back to reference Carter CA, Oronsky BT, Roswarski J, Oronsky AL, Oronsky N, Scicinski J et al (2017) No patient left behind: the promise of immune priming with epigenetic agents. Oncoimmunology 6(10):e1315486PubMedPubMedCentral Carter CA, Oronsky BT, Roswarski J, Oronsky AL, Oronsky N, Scicinski J et al (2017) No patient left behind: the promise of immune priming with epigenetic agents. Oncoimmunology 6(10):e1315486PubMedPubMedCentral
5.
go back to reference Jones PA, Ohtani H, Chakravarthy A, De Carvalho DD (2019) Epigenetic therapy in immune-oncology. Nat Rev Cancer 19(3):151–161PubMed Jones PA, Ohtani H, Chakravarthy A, De Carvalho DD (2019) Epigenetic therapy in immune-oncology. Nat Rev Cancer 19(3):151–161PubMed
6.
go back to reference Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF, Zheng Z et al (2013) Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother 36(2):133–151PubMedPubMedCentral Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF, Zheng Z et al (2013) Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother 36(2):133–151PubMedPubMedCentral
7.
go back to reference Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA (2010) Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 18(4):843–851PubMedPubMedCentral Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA (2010) Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 18(4):843–851PubMedPubMedCentral
8.
go back to reference Liu S, Matsuzaki J, Wei L, Tsuji T, Battaglia S, Hu Q et al (2019) Efficient identification of neoantigen-specific T-cell responses in advanced human ovarian cancer. J Immunother Cancer 7(1):156PubMedPubMedCentral Liu S, Matsuzaki J, Wei L, Tsuji T, Battaglia S, Hu Q et al (2019) Efficient identification of neoantigen-specific T-cell responses in advanced human ovarian cancer. J Immunother Cancer 7(1):156PubMedPubMedCentral
10.
go back to reference Gjerstorff MF, Andersen MH, Ditzel HJ (2015) Oncogenic cancer/testis antigens: prime candidates for immunotherapy. Oncotarget 6(18):15772–15787PubMedPubMedCentral Gjerstorff MF, Andersen MH, Ditzel HJ (2015) Oncogenic cancer/testis antigens: prime candidates for immunotherapy. Oncotarget 6(18):15772–15787PubMedPubMedCentral
11.
go back to reference Scanlan MJ, Simpson AJ, Old LJ (2004) The cancer/testis genes: review, standardization, and commentary. Cancer Immun 4:1PubMed Scanlan MJ, Simpson AJ, Old LJ (2004) The cancer/testis genes: review, standardization, and commentary. Cancer Immun 4:1PubMed
12.
go back to reference Maus MV, Plotkin J, Jakka G, Stewart-Jones G, Riviere I, Merghoub T et al (2016) An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity. Mol Ther Oncolytics 3:1–9PubMed Maus MV, Plotkin J, Jakka G, Stewart-Jones G, Riviere I, Merghoub T et al (2016) An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity. Mol Ther Oncolytics 3:1–9PubMed
13.
go back to reference Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D, Wu G et al (2015) Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov 5(12):1282–1295PubMedPubMedCentral Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D, Wu G et al (2015) Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov 5(12):1282–1295PubMedPubMedCentral
14.
go back to reference Rapoport AP, Stadtmauer EA, Binder-Scholl GK, Goloubeva O, Vogl DT, Lacey SF et al (2015) NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med 21(8):914–921PubMedPubMedCentral Rapoport AP, Stadtmauer EA, Binder-Scholl GK, Goloubeva O, Vogl DT, Lacey SF et al (2015) NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med 21(8):914–921PubMedPubMedCentral
15.
go back to reference Hegde M, Mukherjee M, Grada Z, Pignata A, Landi D, Navai SA et al (2016) Tandem CAR T cells targeting HER2 and IL13Ralpha2 mitigate tumor antigen escape. J Clin Invest 126(8):3036–3052PubMedPubMedCentral Hegde M, Mukherjee M, Grada Z, Pignata A, Landi D, Navai SA et al (2016) Tandem CAR T cells targeting HER2 and IL13Ralpha2 mitigate tumor antigen escape. J Clin Invest 126(8):3036–3052PubMedPubMedCentral
16.
go back to reference Massa C, Seliger B (2019) The tumor microenvironment: thousand obstacles for effector T cells. Cell Immunol 343:103730PubMed Massa C, Seliger B (2019) The tumor microenvironment: thousand obstacles for effector T cells. Cell Immunol 343:103730PubMed
17.
go back to reference John LB, Devaud C, Duong CP, Yong CS, Beavis PA, Haynes NM et al (2013) Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin Cancer Res 19(20):5636–5646PubMed John LB, Devaud C, Duong CP, Yong CS, Beavis PA, Haynes NM et al (2013) Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin Cancer Res 19(20):5636–5646PubMed
18.
go back to reference Kloss CC, Lee J, Zhang A, Chen F, Melenhorst JJ, Lacey SF et al (2018) Dominant-negative TGF-beta receptor enhances PSMA-targeted human CAR T cell proliferation and augments prostate cancer eradication. Mol Ther 26(7):1855–1866PubMedPubMedCentral Kloss CC, Lee J, Zhang A, Chen F, Melenhorst JJ, Lacey SF et al (2018) Dominant-negative TGF-beta receptor enhances PSMA-targeted human CAR T cell proliferation and augments prostate cancer eradication. Mol Ther 26(7):1855–1866PubMedPubMedCentral
19.
go back to reference Feinberg AP, Ohlsson R, Henikoff S (2006) The epigenetic progenitor origin of human cancer. Nat Rev Genet 7(1):21–33PubMed Feinberg AP, Ohlsson R, Henikoff S (2006) The epigenetic progenitor origin of human cancer. Nat Rev Genet 7(1):21–33PubMed
20.
go back to reference Chatterjee A, Rodger EJ, Eccles MR (2018) Epigenetic drivers of tumourigenesis and cancer metastasis. Semin Cancer Biol 51:149–159PubMed Chatterjee A, Rodger EJ, Eccles MR (2018) Epigenetic drivers of tumourigenesis and cancer metastasis. Semin Cancer Biol 51:149–159PubMed
21.
go back to reference Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3(6):415–428PubMed Jones PA, Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3(6):415–428PubMed
23.
go back to reference Rodriguez-Paredes M, Esteller M (2011) Cancer epigenetics reaches mainstream oncology. Nat Med 17(3):330–339PubMed Rodriguez-Paredes M, Esteller M (2011) Cancer epigenetics reaches mainstream oncology. Nat Med 17(3):330–339PubMed
25.
go back to reference Cheng Y, He C, Wang M, Ma X, Mo F, Yang S et al (2019) Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials. Signal Transduct Target Ther 4:62PubMedPubMedCentral Cheng Y, He C, Wang M, Ma X, Mo F, Yang S et al (2019) Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials. Signal Transduct Target Ther 4:62PubMedPubMedCentral
26.
go back to reference Sigalotti L, Fratta E, Coral S, Tanzarella S, Danielli R, Colizzi F et al (2004) Intratumor heterogeneity of cancer/testis antigens expression in human cutaneous melanoma is methylation-regulated and functionally reverted by 5-aza-2'-deoxycytidine. Cancer Res 64(24):9167–9171PubMed Sigalotti L, Fratta E, Coral S, Tanzarella S, Danielli R, Colizzi F et al (2004) Intratumor heterogeneity of cancer/testis antigens expression in human cutaneous melanoma is methylation-regulated and functionally reverted by 5-aza-2'-deoxycytidine. Cancer Res 64(24):9167–9171PubMed
27.
go back to reference Weber J, Salgaller M, Samid D, Johnson B, Herlyn M, Lassam N et al (1994) Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-aza-2'-deoxycytidine. Cancer Res 54(7):1766–1771PubMed Weber J, Salgaller M, Samid D, Johnson B, Herlyn M, Lassam N et al (1994) Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-aza-2'-deoxycytidine. Cancer Res 54(7):1766–1771PubMed
28.
go back to reference Fratta E, Coral S, Covre A, Parisi G, Colizzi F, Danielli R et al (2011) The biology of cancer testis antigens: putative function, regulation and therapeutic potential. Mol Oncol 5(2):164–182PubMedPubMedCentral Fratta E, Coral S, Covre A, Parisi G, Colizzi F, Danielli R et al (2011) The biology of cancer testis antigens: putative function, regulation and therapeutic potential. Mol Oncol 5(2):164–182PubMedPubMedCentral
29.
go back to reference Srivastava P, Paluch BE, Matsuzaki J, James SR, Collamat-Lai G, Taverna P et al (2015) Immunomodulatory action of the DNA methyltransferase inhibitor SGI-110 in epithelial ovarian cancer cells and xenografts. Epigenetics 10(3):237–246PubMedPubMedCentral Srivastava P, Paluch BE, Matsuzaki J, James SR, Collamat-Lai G, Taverna P et al (2015) Immunomodulatory action of the DNA methyltransferase inhibitor SGI-110 in epithelial ovarian cancer cells and xenografts. Epigenetics 10(3):237–246PubMedPubMedCentral
30.
go back to reference Heninger E, Krueger TE, Thiede SM, Sperger JM, Byers BL, Kircher MR et al (2016) Inducible expression of cancer-testis antigens in human prostate cancer. Oncotarget 7(51):84359–84374PubMedPubMedCentral Heninger E, Krueger TE, Thiede SM, Sperger JM, Byers BL, Kircher MR et al (2016) Inducible expression of cancer-testis antigens in human prostate cancer. Oncotarget 7(51):84359–84374PubMedPubMedCentral
31.
go back to reference Karpf AR, Lasek AW, Ririe TO, Hanks AN, Grossman D, Jones DA (2004) Limited gene activation in tumor and normal epithelial cells treated with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. Mol Pharmacol 65(1):18–27PubMed Karpf AR, Lasek AW, Ririe TO, Hanks AN, Grossman D, Jones DA (2004) Limited gene activation in tumor and normal epithelial cells treated with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. Mol Pharmacol 65(1):18–27PubMed
32.
go back to reference Wolff F, Leisch M, Greil R, Risch A, Pleyer L (2017) The double-edged sword of (re)expression of genes by hypomethylating agents: from viral mimicry to exploitation as priming agents for targeted immune checkpoint modulation. Cell Commun Signal 15(1):13PubMedPubMedCentral Wolff F, Leisch M, Greil R, Risch A, Pleyer L (2017) The double-edged sword of (re)expression of genes by hypomethylating agents: from viral mimicry to exploitation as priming agents for targeted immune checkpoint modulation. Cell Commun Signal 15(1):13PubMedPubMedCentral
33.
go back to reference Shahbazian MD, Grunstein M (2007) Functions of site-specific histone acetylation and deacetylation. Annu Rev Biochem 76:75–100PubMed Shahbazian MD, Grunstein M (2007) Functions of site-specific histone acetylation and deacetylation. Annu Rev Biochem 76:75–100PubMed
34.
go back to reference Wischnewski F, Pantel K, Schwarzenbach H (2006) Promoter demethylation and histone acetylation mediate gene expression of MAGE-A1, -A2, -A3, and -A12 in human cancer cells. Mol Cancer Res 4(5):339–349PubMed Wischnewski F, Pantel K, Schwarzenbach H (2006) Promoter demethylation and histone acetylation mediate gene expression of MAGE-A1, -A2, -A3, and -A12 in human cancer cells. Mol Cancer Res 4(5):339–349PubMed
35.
go back to reference Link PA, Gangisetty O, James SR, Woloszynska-Read A, Tachibana M, Shinkai Y et al (2009) Distinct roles for histone methyltransferases G9a and GLP in cancer germ-line antigen gene regulation in human cancer cells and murine embryonic stem cells. Mol Cancer Res 7(6):851–862PubMedPubMedCentral Link PA, Gangisetty O, James SR, Woloszynska-Read A, Tachibana M, Shinkai Y et al (2009) Distinct roles for histone methyltransferases G9a and GLP in cancer germ-line antigen gene regulation in human cancer cells and murine embryonic stem cells. Mol Cancer Res 7(6):851–862PubMedPubMedCentral
36.
go back to reference Sun F, Chan E, Wu Z, Yang X, Marquez VE, Yu Q (2009) Combinatorial pharmacologic approaches target EZH2-mediated gene repression in breast cancer cells. Mol Cancer Ther 8(12):3191–3202PubMedPubMedCentral Sun F, Chan E, Wu Z, Yang X, Marquez VE, Yu Q (2009) Combinatorial pharmacologic approaches target EZH2-mediated gene repression in breast cancer cells. Mol Cancer Ther 8(12):3191–3202PubMedPubMedCentral
37.
go back to reference Zhang M, Liang JQ, Zheng S (2019) Expressional activation and functional roles of human endogenous retroviruses in cancers. Rev Med Virol 29(2):e2025PubMedPubMedCentral Zhang M, Liang JQ, Zheng S (2019) Expressional activation and functional roles of human endogenous retroviruses in cancers. Rev Med Virol 29(2):e2025PubMedPubMedCentral
39.
go back to reference Daskalakis M, Brocks D, Sheng YH, Islam MS, Ressnerova A, Assenov Y et al (2018) Reactivation of endogenous retroviral elements via treatment with DNMT- and HDAC-inhibitors. Cell Cycle 17(7):811–822PubMedPubMedCentral Daskalakis M, Brocks D, Sheng YH, Islam MS, Ressnerova A, Assenov Y et al (2018) Reactivation of endogenous retroviral elements via treatment with DNMT- and HDAC-inhibitors. Cell Cycle 17(7):811–822PubMedPubMedCentral
40.
go back to reference Krishnamurthy J, Rabinovich BA, Mi T, Switzer KC, Olivares S, Maiti SN et al (2015) Genetic engineering of T cells to target HERV-K, an ancient retrovirus on melanoma. Clin Cancer Res 21(14):3241–3251PubMedPubMedCentral Krishnamurthy J, Rabinovich BA, Mi T, Switzer KC, Olivares S, Maiti SN et al (2015) Genetic engineering of T cells to target HERV-K, an ancient retrovirus on melanoma. Clin Cancer Res 21(14):3241–3251PubMedPubMedCentral
41.
go back to reference 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(2):249–256PubMed 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(2):249–256PubMed
42.
go back to reference Garrido F (2019) MHC/HLA class I loss in cancer cells. Adv Exp Med Biol 1151:15–78PubMed Garrido F (2019) MHC/HLA class I loss in cancer cells. Adv Exp Med Biol 1151:15–78PubMed
43.
go back to reference Campoli M, Ferrone S (2008) HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance. Oncogene 27(45):5869–5885PubMedPubMedCentral Campoli M, Ferrone S (2008) HLA antigen changes in malignant cells: epigenetic mechanisms and biologic significance. Oncogene 27(45):5869–5885PubMedPubMedCentral
44.
go back to reference Luo N, Nixon MJ, Gonzalez-Ericsson PI, Sanchez V, Opalenik SR, Li H et al (2018) DNA methyltransferase inhibition upregulates MHC-I to potentiate cytotoxic T lymphocyte responses in breast cancer. Nat Commun 9(1):248PubMedPubMedCentral Luo N, Nixon MJ, Gonzalez-Ericsson PI, Sanchez V, Opalenik SR, Li H et al (2018) DNA methyltransferase inhibition upregulates MHC-I to potentiate cytotoxic T lymphocyte responses in breast cancer. Nat Commun 9(1):248PubMedPubMedCentral
45.
go back to reference Chiappinelli KB, Strissel PL, Desrichard A, Li H, Henke C, Akman B et al (2015) Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162(5):974–986PubMedPubMedCentral Chiappinelli KB, Strissel PL, Desrichard A, Li H, Henke C, Akman B et al (2015) Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162(5):974–986PubMedPubMedCentral
46.
go back to reference Roulois D, Loo Yau H, Singhania R, Wang Y, Danesh A, Shen SY et al (2015) DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell 162(5):961–973PubMedPubMedCentral Roulois D, Loo Yau H, Singhania R, Wang Y, Danesh A, Shen SY et al (2015) DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell 162(5):961–973PubMedPubMedCentral
47.
go back to reference Li H, Chiappinelli KB, Guzzetta AA, Easwaran H, Yen RW, Vatapalli R et al (2014) Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget 5(3):587–598PubMedPubMedCentral Li H, Chiappinelli KB, Guzzetta AA, Easwaran H, Yen RW, Vatapalli R et al (2014) Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget 5(3):587–598PubMedPubMedCentral
48.
go back to reference Stone ML, Chiappinelli KB, Li H, Murphy LM, Travers ME, Topper MJ et al (2017) Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden. Proc Natl Acad Sci USA 114(51):E10981–E10990PubMed Stone ML, Chiappinelli KB, Li H, Murphy LM, Travers ME, Topper MJ et al (2017) Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden. Proc Natl Acad Sci USA 114(51):E10981–E10990PubMed
49.
go back to reference Peng D, Kryczek I, Nagarsheth N, Zhao L, Wei S, Wang W et al (2015) Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy. Nature 527(7577):249–253PubMedPubMedCentral Peng D, Kryczek I, Nagarsheth N, Zhao L, Wei S, Wang W et al (2015) Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy. Nature 527(7577):249–253PubMedPubMedCentral
50.
go back to reference Kim K, Skora AD, Li Z, Liu Q, Tam AJ, Blosser RL et al (2014) Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells. Proc Natl Acad Sci USA 111(32):11774–11779PubMed Kim K, Skora AD, Li Z, Liu Q, Tam AJ, Blosser RL et al (2014) Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells. Proc Natl Acad Sci USA 111(32):11774–11779PubMed
51.
go back to reference Zhou J, Yao Y, Shen Q, Li G, Hu L, Zhang X (2017) Demethylating agent decitabine disrupts tumor-induced immune tolerance by depleting myeloid-derived suppressor cells. J Cancer Res Clin Oncol 143(8):1371–1380PubMed Zhou J, Yao Y, Shen Q, Li G, Hu L, Zhang X (2017) Demethylating agent decitabine disrupts tumor-induced immune tolerance by depleting myeloid-derived suppressor cells. J Cancer Res Clin Oncol 143(8):1371–1380PubMed
52.
go back to reference Terracina KP, Graham LJ, Payne KK, Manjili MH, Baek A, Damle SR et al (2016) DNA methyltransferase inhibition increases efficacy of adoptive cellular immunotherapy of murine breast cancer. Cancer Immunol Immunother 65(9):1061–1073PubMedPubMedCentral Terracina KP, Graham LJ, Payne KK, Manjili MH, Baek A, Damle SR et al (2016) DNA methyltransferase inhibition increases efficacy of adoptive cellular immunotherapy of murine breast cancer. Cancer Immunol Immunother 65(9):1061–1073PubMedPubMedCentral
53.
go back to reference Lal G, Zhang N, van der Touw W, Ding Y, Ju W, Bottinger EP et al (2009) Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J Immunol 182(1):259–273PubMedPubMedCentral Lal G, Zhang N, van der Touw W, Ding Y, Ju W, Bottinger EP et al (2009) Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J Immunol 182(1):259–273PubMedPubMedCentral
54.
go back to reference Costantini B, Kordasti SY, Kulasekararaj AG, Jiang J, Seidl T, Abellan PP et al (2013) The effects of 5-azacytidine on the function and number of regulatory T cells and T-effectors in myelodysplastic syndrome. Haematologica 98(8):1196–1205PubMedPubMedCentral Costantini B, Kordasti SY, Kulasekararaj AG, Jiang J, Seidl T, Abellan PP et al (2013) The effects of 5-azacytidine on the function and number of regulatory T cells and T-effectors in myelodysplastic syndrome. Haematologica 98(8):1196–1205PubMedPubMedCentral
55.
go back to reference Wang D, Quiros J, Mahuron K, Pai CC, Ranzani V, Young A et al (2018) Targeting EZH2 reprograms intratumoral regulatory T cells to Enhance cancer immunity. Cell Rep 23(11):3262–3274PubMedPubMedCentral Wang D, Quiros J, Mahuron K, Pai CC, Ranzani V, Young A et al (2018) Targeting EZH2 reprograms intratumoral regulatory T cells to Enhance cancer immunity. Cell Rep 23(11):3262–3274PubMedPubMedCentral
56.
go back to reference Adeegbe DO, Liu Y, Lizotte PH, Kamihara Y, Aref AR, Almonte C et al (2017) Synergistic immunostimulatory effects and therapeutic benefit of combined histone deacetylase and bromodomain inhibition in non-small cell lung cancer. Cancer Discov 7(8):852–867PubMedPubMedCentral Adeegbe DO, Liu Y, Lizotte PH, Kamihara Y, Aref AR, Almonte C et al (2017) Synergistic immunostimulatory effects and therapeutic benefit of combined histone deacetylase and bromodomain inhibition in non-small cell lung cancer. Cancer Discov 7(8):852–867PubMedPubMedCentral
57.
go back to reference Stubig T, Badbaran A, Luetkens T, Hildebrandt Y, Atanackovic D, Binder TM et al (2014) 5-azacytidine promotes an inhibitory T-cell phenotype and impairs immune mediated antileukemic activity. Mediators Inflamm 2014:418292PubMedPubMedCentral Stubig T, Badbaran A, Luetkens T, Hildebrandt Y, Atanackovic D, Binder TM et al (2014) 5-azacytidine promotes an inhibitory T-cell phenotype and impairs immune mediated antileukemic activity. Mediators Inflamm 2014:418292PubMedPubMedCentral
58.
go back to reference Ghoneim HE, Fan Y, Moustaki A, Abdelsamed HA, Dash P, Dogra P et al (2017) De novo epigenetic programs inhibit PD-1 blockade-mediated T cell rejuvenation. Cell 170(1):142–57e19PubMedPubMedCentral Ghoneim HE, Fan Y, Moustaki A, Abdelsamed HA, Dash P, Dogra P et al (2017) De novo epigenetic programs inhibit PD-1 blockade-mediated T cell rejuvenation. Cell 170(1):142–57e19PubMedPubMedCentral
59.
go back to reference Guo ZS, Hong JA, Irvine KR, Chen GA, Spiess PJ, Liu Y et al (2006) De novo induction of a cancer/testis antigen by 5-aza-2'-deoxycytidine augments adoptive immunotherapy in a murine tumor model. Cancer Res 66(2):1105–1113PubMedPubMedCentral Guo ZS, Hong JA, Irvine KR, Chen GA, Spiess PJ, Liu Y et al (2006) De novo induction of a cancer/testis antigen by 5-aza-2'-deoxycytidine augments adoptive immunotherapy in a murine tumor model. Cancer Res 66(2):1105–1113PubMedPubMedCentral
60.
go back to reference Kunert A, van Brakel M, van Steenbergen-Langeveld S, da Silva M, Coulie PG, Lamers C et al (2016) MAGE-C2-specific TCRs combined with epigenetic drug-enhanced antigenicity yield robust and tumor-selective T cell responses. J Immunol 197(6):2541–2552PubMed Kunert A, van Brakel M, van Steenbergen-Langeveld S, da Silva M, Coulie PG, Lamers C et al (2016) MAGE-C2-specific TCRs combined with epigenetic drug-enhanced antigenicity yield robust and tumor-selective T cell responses. J Immunol 197(6):2541–2552PubMed
61.
go back to reference Chou J, Voong LN, Mortales CL, Towlerton AM, Pollack SM, Chen X et al (2012) Epigenetic modulation to enable antigen-specific T-cell therapy of colorectal cancer. J Immunother 35(2):131–141PubMedPubMedCentral Chou J, Voong LN, Mortales CL, Towlerton AM, Pollack SM, Chen X et al (2012) Epigenetic modulation to enable antigen-specific T-cell therapy of colorectal cancer. J Immunother 35(2):131–141PubMedPubMedCentral
62.
go back to reference Natsume A, Wakabayashi T, Tsujimura K, Shimato S, Ito M, Kuzushima K et al (2008) The DNA demethylating agent 5-aza-2'-deoxycytidine activates NY-ESO-1 antigenicity in orthotopic human glioma. Int J Cancer 122(11):2542–2553PubMed Natsume A, Wakabayashi T, Tsujimura K, Shimato S, Ito M, Kuzushima K et al (2008) The DNA demethylating agent 5-aza-2'-deoxycytidine activates NY-ESO-1 antigenicity in orthotopic human glioma. Int J Cancer 122(11):2542–2553PubMed
63.
go back to reference Yan M, Himoudi N, Basu BP, Wallace R, Poon E, Adams S et al (2011) Increased PRAME antigen-specific killing of malignant cell lines by low avidity CTL clones, following treatment with 5-Aza-2'-Deoxycytidine. Cancer Immunol Immunother 60(9):1243–1255PubMed Yan M, Himoudi N, Basu BP, Wallace R, Poon E, Adams S et al (2011) Increased PRAME antigen-specific killing of malignant cell lines by low avidity CTL clones, following treatment with 5-Aza-2'-Deoxycytidine. Cancer Immunol Immunother 60(9):1243–1255PubMed
64.
go back to reference Vo DD, Prins RM, Begley JL, Donahue TR, Morris LF, Bruhn KW et al (2009) Enhanced antitumor activity induced by adoptive T-cell transfer and adjunctive use of the histone deacetylase inhibitor LAQ824. Cancer Res 69(22):8693–8699PubMedPubMedCentral Vo DD, Prins RM, Begley JL, Donahue TR, Morris LF, Bruhn KW et al (2009) Enhanced antitumor activity induced by adoptive T-cell transfer and adjunctive use of the histone deacetylase inhibitor LAQ824. Cancer Res 69(22):8693–8699PubMedPubMedCentral
65.
go back to reference Kailayangiri S, Altvater B, Lesch S, Balbach S, Gottlich C, Kuhnemundt J et al (2019) EZH2 inhibition in Ewing sarcoma upregulates GD2 expression for targeting with gene-modified T cells. Mol Ther 27(5):933–946PubMedPubMedCentral Kailayangiri S, Altvater B, Lesch S, Balbach S, Gottlich C, Kuhnemundt J et al (2019) EZH2 inhibition in Ewing sarcoma upregulates GD2 expression for targeting with gene-modified T cells. Mol Ther 27(5):933–946PubMedPubMedCentral
Metadata
Title
Augmenting engineered T-cell strategies in solid cancers through epigenetic priming
Authors
Aaraby Y. Nielsen
Maria Ormhøj
Sofie Traynor
Morten F. Gjerstorff
Publication date
01-11-2020
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 11/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-020-02661-1

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