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Immunotherapeutics – Review

Adoptive tumor infiltrating lymphocytes cell therapy for cervical cancer

, , , , ORCID Icon &
Article: 2060019 | Received 01 Dec 2021, Accepted 26 Mar 2022, Published online: 25 Apr 2022

References

  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–11. doi:10.3322/caac.21492.
  • Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32. doi:10.3322/caac.21338.
  • Tewari KS, Sill MW, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet. 2017;390(10103):1654–63. doi:10.1016/s0140-6736(17)31607-0. PMID:Pmc5714293.
  • Hong M, Clubb JD, Chen YY. Engineering CAR-T cells for next-generation cancer therapy. Cancer Cell. 2020;38(4):473–88. doi:10.1016/j.ccell.2020.07.005.
  • Wu Y, Chen W, Xu ZP, Gu W. PD-L1 distribution and perspective for cancer immunotherapy-blockade, knockdown, or inhibition. Front Immunol. 2019;10:2022. doi:10.3389/fimmu.2019.02022. PMID:Pmc6718566.
  • Gorabi AM, Hajighasemi S, Sathyapalan T, Sahebkar A. Cell transfer-based immunotherapies in cancer: a review. IUBMB Life. 2020;72(4):790–800. doi:10.1002/iub.2180.
  • Strizova Z, Bartunkova J, Smrz D. The challenges of adoptive cell transfer in the treatment of human renal cell carcinoma. Cancer Immunol Immunother. 2019;68(11):1831–38. doi:10.1007/s00262-019-02359-z.
  • Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12–19. doi:10.1002/(sici)1096-9896(199909)189:1<12:aid-path431>3.0.co;2-f.
  • Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC. Human papillomavirus and cervical cancer. Lancet. 2013;382(9895):889–99. doi:10.1016/s0140-6736(13)60022-7.
  • Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 1990;63(6):1129–36. doi:10.1016/0092-8674(90)90409-8.
  • Ganti K, Broniarczyk J, Manoubi W, Massimi P, Mittal S, Pim D, Szalmas A, Thatte J, Thomas M, Tomaić V, et al. The human papillomavirus E6 PDZ binding motif: from life cycle to malignancy. Viruses. 2015;7(7):3530–51. doi:10.3390/v7072785. PMID:Pmc4517114.
  • Dyson N, Howley PM, Münger K, Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science. 1989;243(4893):934–37. doi:10.1126/science.2537532.
  • Zhou F, Chen J, Zhao KN. Human papillomavirus 16-encoded E7 protein inhibits IFN-γ-mediated MHC class I antigen presentation and CTL-induced lysis by blocking IRF-1 expression in mouse keratinocytes. J Gen Virol. 2013;94(Pt 11):2504–14. doi:10.1099/vir.0.054486-0.
  • Kim TJ, Jin HT, Hur SY, Yang HG, Seo YB, Hong SR, Lee CW, Kim S, Woo JW, Park KS, et al. Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients. Nat Commun. 2014;5:5317. PMID:PMC4220493 which is developing GX-188E vaccine. The remaining authors declare no competing financial interests. doi:10.1038/ncomms6317.
  • Liao SJ, Deng DR, Zeng D, Zhang L, Hu XJ, Zhang WN, Li L, Jiang XF, Wang CY, Zhou JF, et al. HPV16 E5 peptide vaccine in treatment of cervical cancer in vitro and in vivo. J Huazhong Univ Sci Technolog Med Sci. 2013;33(5):735–42. doi:10.1007/s11596-013-1189-5.
  • Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp CA, et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. a preliminary report. N Engl J Med. 1988;319(25):1676–80. doi:10.1056/nejm198812223192527.
  • Rosenberg SA, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science. 1986;233(4770):1318–21. doi:10.1126/science.3489291.
  • Simoni Y, Becht E, Fehlings M, Loh CY, Koo SL, Teng KWW, Yeong JPS, Nahar R, Zhang T, Kared H, et al. Bystander CD8(+) T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature. 2018;557(7706):575–79. doi:10.1038/s41586-018-0130-2.
  • Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, Robbins PF, Huang J, Citrin DE, Leitman SF, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008;26(32):5233–39. doi:10.1200/jco.2008.16.5449. PMID:Pmc2652090.
  • Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, Citrin DE, Restifo NP, Robbins PF, Wunderlich JR, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011;17(13):4550–57. doi:10.1158/1078-0432.ccr-11-0116. PMID:Pmc3131487.
  • Merhavi-Shoham E, Itzhaki O, Markel G, Schachter J, Besser MJ. Adoptive cell therapy for metastatic melanoma. Cancer J. 2017;23(1):48–53. doi:10.1097/ppo.0000000000000240.
  • Schalper KA, Brown J, Carvajal-Hausdorf D, McLaughlin J, Velcheti V, Syrigos KN, Herbst RS, Rimm DL. Objective measurement and clinical significance of TILs in non-small cell lung cancer. J Natl Cancer Inst. 2015;107(3). doi:10.1093/jnci/dju435. PMID:Pmc4565530.
  • Stevanović S, Draper LM, Langhan MM, Campbell TE, Kwong ML, Wunderlich JR, Dudley ME, Yang JC, Sherry RM, Kammula US, et al. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J Clin Oncol. 2015;33(14):1543–50. doi:10.1200/jco.2014.58.9093. PMID:PMC4417725 online at Author contributions are found at the end of this article.
  • Stevanović S, Pasetto A, Helman SR, Gartner JJ, Prickett TD, Howie B, Robins HS, Robbins PF, Klebanoff CA, Rosenberg SA, et al. Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. Science. 2017;356(6334):200–05. doi:10.1126/science.aak9510. PMID:Pmc6295311.
  • Stevanović S, Helman SR, Wunderlich JR, Langhan MM, Doran SL, Kwong MLM, Somerville RPT, Klebanoff CA, Kammula US, Sherry RM, et al. A phase II study of tumor-infiltrating lymphocyte therapy for human papillomavirus-associated epithelial cancers. Clin Cancer Res. 2019;25(5):1486–93. doi:10.1158/1078-0432.ccr-18-2722. PMID:Pmc6397671.
  • Rohaan MW, Wilgenhof S, Haanen J. Adoptive cellular therapies: the current landscape. Virchows Arch. 2019;474(4):449–61. doi:10.1007/s00428-018-2484-0. PMID:Pmc6447513.
  • Faltas BM, Prandi D, Tagawa ST, Molina AM, Nanus DM, Sternberg C, Rosenberg J, Mosquera JM, Robinson B, Elemento O, et al. Clonal evolution of chemotherapy-resistant urothelial carcinoma. Nat Genet. 2016;48(12):1490–99. doi:10.1038/ng.3692. PMID:Pmc5549141.
  • Blank CU, Haanen JB, Ribas A, Schumacher TN. Cancer Immunology. the “cancer immunogram”. Science. 2016;352(6286):658–60. doi:10.1126/science.aaf2834.
  • Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, Zhang W, Luoma A, Giobbie-Hurder A, Peter L, et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017;547(7662):217–21. doi:10.1038/nature22991. PMID:Pmc5577644.
  • Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348(6230):69–74. doi:10.1126/science.aaa4971.
  • Chacon JA, Sarnaik AA, Chen JQ, Creasy C, Kale C, Robinson J, Weber J, Hwu P, Pilon-Thomas S, Radvanyi L. Manipulating the tumor microenvironment ex vivo for enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy. Clin Cancer Res. 2015;21(3):611–21. doi:10.1158/1078-0432.ccr-14-1934. PMID:Pmc4315752.
  • Ye Q, Song DG, Poussin M, Yamamoto T, Best A, Li C, Coukos G, Powell DJ Jr. CD137 accurately identifies and enriches for naturally occurring tumor-reactive T cells in tumor. Clin Cancer Res. 2014;20(1):44–55. doi:10.1158/1078-0432.ccr-13-0945. PMID:Pmc3947326.
  • Radvanyi LG, Bernatchez C, Zhang M, Fox PS, Miller P, Chacon J, Wu R, Lizee G, Mahoney S, Alvarado G, et al. Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Clin Cancer Res. 2012;18(24):6758–70. doi:10.1158/1078-0432.ccr-12-1177. PMID:Pmc3525747.
  • Wang A, Chandran S, Shah SA, Chiu Y, Paria BC, Aghamolla T, Alvarez-Downing MM, Lee CC, Singh S, Li T, et al. The stoichiometric production of IL-2 and IFN-γ mRNA defines memory T cells that can self-renew after adoptive transfer in humans. Sci Transl Med. 2012;4(149):149ra120. doi:10.1126/scitranslmed.3004306. PMID:Pmc6453124.
  • Tran KQ, Zhou J, Durflinger KH, Langhan MM, Shelton TE, Wunderlich JR, Robbins PF, Rosenberg SA, Dudley ME. Minimally cultured tumor-infiltrating lymphocytes display optimal characteristics for adoptive cell therapy. J Immunother (1991). 2008;31(8):742–51. doi:10.1097/CJI.0b013e31818403d5. PMID:Pmc2614999.
  • Dudley ME, Gross CA, Somerville RP, Hong Y, Schaub NP, Rosati SF, White DE, Nathan D, Restifo NP, Steinberg SM, et al. Randomized selection design trial evaluating CD8±enriched versus unselected tumor-infiltrating lymphocytes for adoptive cell therapy for patients with melanoma. J Clin Oncol. 2013;31(17):2152–59. doi:10.1200/jco.2012.46.6441. PMID:PMC3731980 found at the end of this article.
  • Pilon-Thomas S, Kuhn L, Ellwanger S, Janssen W, Royster E, Marzban S, Kudchadkar R, Zager J, Gibney G, Sondak VK, et al. Efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes after lymphopenia induction for metastatic melanoma. J Immunother (1991). 2012;35(8):615–20. doi:10.1097/CJI.0b013e31826e8f5f. PMID:4467830.
  • O’-Shea JJ, Paul WE. Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science. 2010;327(5969):1098–102. doi:10.1126/science.1178334. PMID:2997673.
  • Qui HZ, Hagymasi AT, Bandyopadhyay S, St Rose MC, Ramanarasimhaiah R, Ménoret A, Mittler RS, Gordon SM, Reiner SL, Vella AT, et al. CD134 plus CD137 dual costimulation induces Eomesodermin in CD4 T cells to program cytotoxic Th1 differentiation. J Immunol. 2011;187(7):3555–64. doi:10.4049/jimmunol.1101244. PMID:3178659.
  • Nakanishi Y, Lu B, Gerard C, Iwasaki A. CD8(+) T lymphocyte mobilization to virus-infected tissue requires CD4(+) T-cell help. Nature. 2009;462(7272):510–13. doi:10.1038/nature08511. PMID:2789415.
  • Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS, et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014;344(6184):641–45. doi:10.1126/science.1251102.
  • Veatch JR, Lee SM, Fitzgibbon M, Chow IT, Jesernig B, Schmitt T, Kong YY, Kargl J, Houghton AM, Thompson JA, et al. Tumor-Infiltrating BRAFV600E-specific CD4+ T cells correlated with complete clinical response in melanoma. J Clin Invest. 2018;128(4):1563–68. doi:10.1172/jci98689. PMID:5873881.
  • Zacharakis N, Chinnasamy H, Black M, Xu H, Lu YC, Zheng Z, Pasetto A, Langhan M, Shelton T, Prickett T, et al. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat Med. 2018;24(6):724–30. doi:10.1038/s41591-018-0040-8. PMID:6348479.
  • Tran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L, Pasetto A, Zheng Z, Ray S, Groh EM, et al. T-cell transfer therapy targeting mutant KRAS in cancer. N Engl J Med. 2016;375(23):2255–62. doi:10.1056/NEJMoa1609279. PMID:5178827.
  • Zhang AW, McPherson A, Milne K, Kroeger DR, Hamilton PT, Miranda A, Funnell T, Little N, de Souza CPE, Laan S, et al. Interfaces of malignant and immunologic clonal dynamics in ovarian cancer. Cell. 2018;173(7):1755–69.e1722. doi:10.1016/j.cell.2018.03.073.
  • Donia M, Kjeldsen JW, Andersen R, Westergaard MCW, Bianchi V, Legut M, Attaf M, Szomolay B, Ott S, Dolton G, et al. PD-1(+) polyfunctional T cells dominate the periphery after tumor-infiltrating lymphocyte therapy for cancer. Clin Cancer Res. 2017;23(19):5779–88. doi:10.1158/1078-0432.ccr-16-1692. PMID:7115919.
  • de Vos van Steenwijk PJ, Heusinkveld M, Ramwadhdoebe TH, Löwik MJ, van der Hulst JM, Goedemans R, Piersma SJ, Kenter GG, van der Burg SH. An unexpectedly large polyclonal repertoire of HPV-specific T cells is poised for action in patients with cervical cancer. Cancer Res. 2010;70(7):2707–17. doi:10.1158/0008-5472.can-09-4299.
  • Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, Porta-Pardo E, Gao GF, Plaisier CL, Eddy JA, et al. The immune landscape of cancer. Immunity. 2018;48(4):812–30.e814. doi:10.1016/j.immuni.2018.03.023. PMID:5982584.
  • Adurthi S, Mukherjee G, Krishnamurthy H, Sudhir K, Bafna UD, Umadevi K, Jayshree RS. Functional tumor infiltrating TH1 and TH2 effectors in large early-stage cervical cancer are suppressed by regulatory T cells. Int J Gynecol Cancer. 2012;22(7):1130–37. doi:10.1097/IGC.0b013e318262aa53.
  • Radvanyi LG. Tumor-infiltrating lymphocyte therapy: addressing prevailing questions. Cancer J. 2015;21(6):450–64. doi:10.1097/ppo.0000000000000162.
  • Schumacher TN, Scheper W, Kvistborg P. Cancer neoantigens. Annu Rev Immunol. 2019;37:173–200. doi:10.1146/annurev-immunol-042617-053402.
  • Tang Y, Zhang AXJ, Chen G, Wu Y, Gu W. Prognostic and therapeutic TILs of cervical cancer-current advances and future perspectives. Mol Ther Oncolytics. 2021;22:410–30. PMID:Pmc8430272. doi:10.1016/j.omto.2021.07.006.
  • Moon EK, Carpenito C, Sun J, Wang LC, Kapoor V, Predina J, Powell DJ Jr., Riley JL, June CH, Albelda SM. Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human T cells expressing a mesothelin-specific chimeric antibody receptor. Clin Cancer Res. 2011;17(14):4719–30. doi:10.1158/1078-0432.ccr-11-0351. PMID:3612507.
  • Liu YT, Sun ZJ. Turning cold tumors into hot tumors by improving T-cell infiltration. Theranostics. 2021;11(11):5365–86. doi:10.7150/thno.58390. PMID:Pmc8039952.
  • Ding N, Zou Z, Sha H, Su S, Qian H, Meng F, Chen F, Du S, Zhou S, Chen H, et al. iRGD synergizes with PD-1 knockout immunotherapy by enhancing lymphocyte infiltration in gastric cancer. Nat Commun. 2019;10(1):1336. doi:10.1038/s41467-019-09296-6. PMID:6430780.
  • Pitt JM, Marabelle A, Eggermont A, Soria JC, Kroemer G, Zitvogel L. Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy. Ann Oncol. 2016;27(8):1482–92. doi:10.1093/annonc/mdw168.
  • Ritthipichai K, Haymaker CL, Martinez M, Aschenbrenner A, Yi X, Zhang M, Kale C, Vence LM, Roszik J, Hailemichael Y, et al. Multifaceted role of BTLA in the control of CD8(+) T-cell fate after antigen encounter. Clin Cancer Res. 2017;23(20):6151–64. doi:10.1158/1078-0432.ccr-16-1217. PMID:5748156.
  • Shang B, Liu Y, Jiang SJ, Liu Y. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis. Sci Rep. 2015;5:15179. PMID:4604472. doi:10.1038/srep15179.
  • Mahadeo KM, Khazal SJ, Abdel-Azim H, Fitzgerald JC, Taraseviciute A, Bollard CM, Tewari P, Duncan C, Traube C, McCall D, et al. Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy. Nat Rev Clin Oncol. 2019;16(1):45–63. doi:10.1038/s41571-018-0075-2. PMID:7096894.
  • Met Ö, Jensen KM, Chamberlain CA, Donia M, Svane IM. Principles of adoptive T cell therapy in cancer. Semin Immunopathol. 2019;41(1):49–58. doi:10.1007/s00281-018-0703-z.
  • Gowrishankar K, Birtwistle L, Micklethwaite K. Manipulating the tumor microenvironment by adoptive cell transfer of CAR T-cells. Mamm Genome. 2018;29(11–12):739–56. doi:10.1007/s00335-018-9756-5.
  • Khalil DN, Smith EL, Brentjens RJ, Wolchok JD. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol. 2016;13(5):273–90. doi:10.1038/nrclinonc.2016.25. PMID:5551685.
  • Frenel JS, Le Tourneau C, O’-Neil B, Ott PA, Piha-Paul SA, Gomez-Roca C, van Brummelen EMJ, Rugo HS, Thomas S, Saraf S, et al. Safety and efficacy of pembrolizumab in advanced, programmed death ligand 1-positive cervical cancer: results from the Phase Ib KEYNOTE-028 trial. J Clin Oncol. 2017;35(36):4035–41. doi:10.1200/jco.2017.74.5471.
  • Yang W, Song Y, Lu YL, Sun JZ, Wang HW. Increased expression of programmed death (PD)-1 and its ligand PD-L1 correlates with impaired cell-mediated immunity in high-risk human papillomavirus-related cervical intraepithelial neoplasia. Immunology. 2013;139(4):513–22. doi:10.1111/imm.12101. PMID:3719068.
  • Feng YC, Ji WL, Yue N, Huang YC, Ma XM. The relationship between the PD-1/PD-L1 pathway and DNA mismatch repair in cervical cancer and its clinical significance. Cancer Manag Res. 2018;10:105–13. PMID:5783151. doi:10.2147/cmar.s152232.
  • Ohaegbulam KC, Assal A, Lazar-Molnar E, Yao Y, Zang X. Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol Med. 2015;21(1):24–33. doi:10.1016/j.molmed.2014.10.009. PMID:4282825.
  • Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, Ha TT, Gajewski TF. Up-Regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med. 2013;5(200):200ra116. doi:10.1126/scitranslmed.3006504. PMID:4136707.
  • Andersen R, Borch TH, Draghi A, Gokuldass A, Rana MAH, Pedersen M, Nielsen M, Kongsted P, Kjeldsen JW, Westergaard MCW, et al. T cells isolated from patients with checkpoint inhibitor-resistant melanoma are functional and can mediate tumor regression. Ann Oncol. 2018;29(7):1575–81. doi:10.1093/annonc/mdy139.
  • Yin H, Guo W, Sun X, Li R, Feng C, Tan Y. Tils and anti-PD1 therapy: an alternative combination therapy for PDL1 negative metastatic cervical cancer. J Immunol Res. 2020;2020:8345235. PMID:Pmc7492938. doi:10.1155/2020/8345235.
  • Fucikova J, Rakova J, Hensler M, Kasikova L, Belicova L, Hladikova K, Truxova I, Skapa P, Laco J, Pecen L, et al. TIM-3 dictates functional orientation of the immune infiltrate in ovarian cancer. Clin Cancer Res. 2019;25(15):4820–31. doi:10.1158/1078-0432.ccr-18-4175.
  • He Y, Yu H, Rozeboom L, Rivard CJ, Ellison K, Dziadziuszko R, Suda K, Ren S, Wu C, Hou L, et al. LAG-3 protein expression in non-small cell lung cancer and its relationship with PD-1/PD-L1 and tumor-infiltrating lymphocytes. J Thorac Oncol. 2017;12(5):814–23. doi:10.1016/j.jtho.2017.01.019.
  • Pedersen M, Westergaard MCW, Milne K, Nielsen M, Borch TH, Poulsen LG, Hendel HW, Kennedy M, Briggs G, Ledoux S, et al. Adoptive cell therapy with tumor-infiltrating lymphocytes in patients with metastatic ovarian cancer: a pilot study. Oncoimmunology. 2018;7(12):e1502905. doi:10.1080/2162402x.2018.1502905. PMID:6279323.
  • Yannelli JR, Wroblewski JM. On the road to a tumor cell vaccine: 20 years of cellular immunotherapy. Vaccine. 2004;23(1):97–113. doi:10.1016/j.vaccine.2003.12.036.
  • Laheru D, Lutz E, Burke J, Biedrzycki B, Solt S, Onners B, Tartakovsky I, Nemunaitis J, Le D, Sugar E, et al. Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res. 2008;14(5):1455–63. doi:10.1158/1078-0432.ccr-07-0371. PMID:2879140.
  • Lutz ER, Wu AA, Bigelow E, Sharma R, Mo G, Soares K, Solt S, Dorman A, Wamwea A, Yager A, et al. Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation. Cancer Immunol Res. 2014;2(7):616–31. doi:10.1158/2326-6066.cir-14-0027. PMID:4082460.
  • Cipponi A, Mercier M, Seremet T, Baurain JF, Théate I, van den Oord J, Stas M, Boon T, Coulie PG, van Baren N. Neogenesis of lymphoid structures and antibody responses occur in human melanoma metastases. Cancer Res. 2012;72(16):3997–4007. doi:10.1158/0008-5472.can-12-1377.
  • Dieu-Nosjean MC, Antoine M, Danel C, Heudes D, Wislez M, Poulot V, Rabbe N, Laurans L, Tartour E, de Chaisemartin L, et al. Long-Term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. J Clin Oncol. 2008;26(27):4410–17. doi:10.1200/jco.2007.15.0284.
  • Lövgren T, Wolodarski M, Wickström S, Edbäck U, Wallin M, Martell E, Markland K, Blomberg P, Nyström M, Lundqvist A, et al. Complete and long-lasting clinical responses in immune checkpoint inhibitor-resistant, metastasized melanoma treated with adoptive T cell transfer combined with DC vaccination. Oncoimmunology. 2020;9(1):1792058. doi:10.1080/2162402x.2020.1792058. PMID:Pmc7458624.
  • Song S, Zhang K, You H, Wang J, Wang Z, Yan C, Liu F. Significant anti-tumour activity of adoptively transferred T cells elicited by intratumoral dendritic cell vaccine injection through enhancing the ratio of CD8(+) T cell/regulatory T cells in tumour. Clin Exp Immunol. 2010;162(1):75–83. doi:10.1111/j.1365-2249.2010.04226.x. PMID:Pmc2990932.
  • Burgers WA, Blanchon L, Pradhan S, de Launoit Y, Kouzarides T, Fuks F. Viral oncoproteins target the DNA methyltransferases. Oncogene. 2007;26(11):1650–55. doi:10.1038/sj.onc.1209950. PMID:3350866.
  • Peng D, Kryczek I, Nagarsheth N, Zhao L, Wei S, Wang W, Sun Y, Zhao E, Vatan L, Szeliga W, et al. Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy. Nature. 2015;527(7577):249–53. doi:10.1038/nature15520. PMID:4779053.
  • Dan H, Zhang S, Zhou Y, Guan Q. DNA methyltransferase inhibitors: catalysts for antitumour immune responses. Onco Targets Ther. 2019;12:10903–16. PMID:Pmc6913319. doi:10.2147/ott.s217767.
  • Covre A, Coral S, Nicolay H, Parisi G, Fazio C, Colizzi F, Fratta E, Di Giacomo AM, Sigalotti L, Natali PG, et al. Antitumor activity of epigenetic immunomodulation combined with CTLA-4 blockade in syngeneic mouse models. Oncoimmunology. 2015;4(8):e1019978. doi:10.1080/2162402x.2015.1019978. PMID:4570131.
  • Saleh MH, Wang L, Goldberg MS. Improving cancer immunotherapy with DNA methyltransferase inhibitors. Cancer Immunol Immunother. 2016;65(7):787–96. doi:10.1007/s00262-015-1776-3.
  • Wang Z, Chen JQ, Liu JL, Qin XG, Huang Y. FDG-PET in diagnosis, staging and prognosis of pancreatic carcinoma: a meta-analysis. World J Gastroenterol. 2013;19(29):4808–17. doi:10.3748/wjg.v19.i29.4808. PMID:3732856.
  • Sahin M, Sahin E, Koksoy S. Regulatory T cells in cancer: an overview and perspectives on cyclooxygenase-2 and Foxp3 DNA methylation. Hum Immunol. 2013;74(9):1061–68. doi:10.1016/j.humimm.2013.05.009.
  • Zhang Y, Maksimovic J, Naselli G, Qian J, Chopin M, Blewitt ME, Oshlack A, Harrison LC. Genome-wide DNA methylation analysis identifies hypomethylated genes regulated by FOXP3 in human regulatory T cells. Blood. 2013;122(16):2823–36. doi:10.1182/blood-2013-02-481788. PMID:3798997.
  • Eckschlager T, Plch J, Stiborova M, Hrabeta J. Histone deacetylase inhibitors as anticancer drugs. Int J Mol Sci. 2017;18(7). doi:10.3390/ijms18071414. PMID:Pmc5535906.
  • Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer. 2012;12(4):237–51. doi:10.1038/nrc3237. PMID:3967236.
  • Cao K, Wang G, Li W, Zhang L, Wang R, Huang Y, Du L, Jiang J, Wu C, He X, et al. Histone deacetylase inhibitors prevent activation-induced cell death and promote anti-tumor immunity. Oncogene. 2015;34(49):5960–70. doi:10.1038/onc.2015.46. PMID:4672172.
  • Agarwal P, Raghavan A, Nandiwada SL, Curtsinger JM, Bohjanen PR, Mueller DL, Mescher MF. Gene regulation and chromatin remodeling by IL-12 and type I IFN in programming for CD8 T cell effector function and memory. J Immunol. 2009;183(3):1695–704. doi:10.4049/jimmunol.0900592. PMID:2893405.
  • Zhang F, Zhou X, DiSpirito JR, Wang C, Wang Y, Shen H. Epigenetic manipulation restores functions of defective CD8+ T cells from chronic viral infection. Mol Ther. 2014;22(9):1698–706. doi:10.1038/mt.2014.91. PMID:4435497.
  • Kroesen M, Gielen P, Brok IC, Armandari I, Hoogerbrugge PM, Adema GJ. HDAC inhibitors and immunotherapy; a double edged sword? Oncotarget. 2014;5(16):6558–72. doi:10.18632/oncotarget.2289. PMID:Pmc4196144.
  • Gomez S, Tabernacki T, Kobyra J, Roberts P, Chiappinelli KB. Combining epigenetic and immune therapy to overcome cancer resistance. Semin Cancer Biol. 2020;65:99–113. PMID:7308208. doi:10.1016/j.semcancer.2019.12.019.