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Potential role of immune cell therapy in gynecological cancer and future promises: a comprehensive review

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Abstract

Gynecological malignancies are most leading causes of death among women worldwide. The high prevalence of gynecologic malignancies remains significant, necessitating to turn the novel treatment approach like immunotherapy, wherein cancer cells are killed by the invasion of immune system. In recent year, immunotherapy has mostly an advanced treatment approach to repressing the tumor cells survival, proliferation, and invasion via the activation of immune systems. Moreover, various types of immune cells including T-cells, B-cells, and dendritic cells are associated with the immunotherapeutic strategy in cancer treatment. Although the significant role of T-cells against cancer is well established, while B-cells and dendritic cells also play an important role against different gynecological cancer by regulating the immune system. This review focuses on that arena and highlight the role of immune cells in the treatment of gynaecological cancer. Various immune cell-based anticancer therapies such as T-cell therapies, Adoptive Cellular transfer, B-cell therapies as well as approaches to Dendritic Cell therapies have been discussed in detail. Furthermore, the clinical settings and future avenues regarding immunotherapy on gynecological cancer have also been reviewed and illuminated in the recent study.

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References

  1. Decker WK, da Silva RF, Sanabria MH, Angelo LS, Guimarães F, Burt BM, et al. Cancer immunotherapy: historical perspective of a clinical revolution and emerging preclinical animal models. Front Immunol. 2017;8:829.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Oiseth SJ, Aziz MS. Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead. J Cancer Metastasis Treat. 2017;3:250–61.

    Article  CAS  Google Scholar 

  3. Halliday GM, Patel A, Hunt MJ, Tefany FJ, Barnetson RS. Spontaneous regression of human melanoma/nonmelanoma skin cancer: association with infiltrating CD4+ T cells. World J Surg. 1995;19:352–8.

    Article  CAS  PubMed  Google Scholar 

  4. Rosenberg SA. Raising the bar: the curative potential of human cancer immunotherapy. Sci Transl Med. 2012;4:127ps8.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Nikanjam M, Mullen J, Yacoub C, Daniels GA. Combination high-dose interleukin-2 and nivolumab for programmed cell death-1 refractory metastatic melanoma: a case series. J Med Case Rep. 2022;16(1):337.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lynam S, Lugade AA, Odunsi K. Immunotherapy for gynecologic cancer: current applications and future directions. Clin Obstet Gynecol. 2020;63(1):48–63.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Quezada SA, Peggs KS, Simpson TR, Allison JP. Shifting the equilibrium in cancer immunoediting: from tumor tolerance to eradication. Immunol Rev. 2011;241(1):104–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jiang G, Wu Q, Li B. Evaluation of immunotherapy efficacy in gynecologic cancer. Front Immunol. 2023;14:1061761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nishio H, Iwata T, Aoki D. Current status of cancer immunotherapy for gynecologic malignancies. Jpn J Clin Oncol. 2021;51(2):167–72.

    Article  PubMed  Google Scholar 

  10. Lorusso D, Ceni V, Daniele G, Pietragalla A, Salutari V, Muratore M, et al. Immunotherapy in gynecological cancers. Explor Target Antitumor Ther. 2021;2(1):48–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Ventriglia J, Paciolla I, Pisano C, Cecere SC, Di Napoli M, Tambaro R, et al. Immunotherapy in ovarian, endometrial and cervical cancer: State of the art and future perspectives. Cancer Treat Rev. 2017;59:109–16.

    Article  CAS  PubMed  Google Scholar 

  12. Ascierto ML, Idowu MO, Zhao Y, Khalak H, Payne KK, Wang XY, Dumur CI, Bedognetti D, Tomei S, Ascierto PA, Shanker A, Bear HD, Wang E, Marincola FM, De Maria A, Manjili MH. Molecular signatures mostly associated with NK cells arepredictive of relapse free survival in breast cancer patients. J Transl Med. 2013;11(1):145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, et al. Type, density, and location of immune cells withinhuman colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.

    Article  CAS  PubMed  Google Scholar 

  14. Ginsburgs VH, Goodill SW. A dance/movement therapy clinical model for women with gynecologic cancer undergoing high dose rate brachytherapy. Am J Dance Ther. 2009;31(2):136–58.

    Article  Google Scholar 

  15. Gonzalez H, Hagerling C, Werb Z. Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes Dev. 2018;32(19–20):1267–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Parrott DV, de Sousa MA, East J. Thymus-dependent areas in the lymphoid organs of neonatally thymectomized mice. J Exp Med. 1966;123:191–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. LeBien TW, Tedder TFB. lymphocytes: how they develop and function. Blood. 2008;112:1570–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chen C, Liu X, Chang CY, Wang HY, Wang RF. The interplay between T cells and cancer: the basis of immunotherapy. Genes. 2023;14:1008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lanza R, Russell DW, Nagy A. Engineering universal cells that evade immune detection. Nat Rev Immunol. 2019;19(12):723–33.

    Article  CAS  PubMed  Google Scholar 

  20. Speiser DE, Ho PC, Verdeil G. Regulatory circuits of T cell function in cancer. Nat Rev Immunol. 2016;16(10):599–611.

    Article  CAS  PubMed  Google Scholar 

  21. Donadon M, Hudspeth K, Cimino M, Di Tommaso L, Preti M, Tentorio P, et al. Increased infiltration of natural killer and T cells in colorectal liver metastases improves patient overall survival. J Gastrointest Surg. 2017;21(8):1226–36.

    Article  PubMed  Google Scholar 

  22. Kumar BV, Connors TJ, Farber DL. Human T cell development, localization, and function throughout life. Immunity. 2018;48:202–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. van den Broek T, Borghans JAM, van Wijk F. The full spectrum of human naive T cells. Nat Rev Immunol. 2018;18(6):363–73.

    Article  PubMed  Google Scholar 

  24. Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol. 2008;8(7):523–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Nikolich-Zugich J, Slifka MK, Messaoudi I. The many important facets of T-cell repertoire diversity. Nat Rev Immunol. 2004;4:123–32.

    Article  CAS  PubMed  Google Scholar 

  26. Wilson IA, Garcia KC. T-cell receptor structure and TCR complexes. Curr Opin Struct Biol. 1997;7:839–48.

    Article  CAS  PubMed  Google Scholar 

  27. Mueller DL, Jenkins MK, Schwartz RH. Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol. 1989;7:445–80.

    Article  CAS  PubMed  Google Scholar 

  28. 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):651–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Legut M, Dolton G, Mian AA, Ottmann OG, Sewell AK. CRISPR-mediated TCR replacement generates superior anticancer transgenic T cells. Blood. 2018;131(3):311–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yuen GJ, Demissie E, Pillai S. B lymphocytes and cancer: a love–hate relationship. Trends in cancer. 2016;2(12):747–57.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Chen Z, Zhu Y, Du R, Pang N, Zhang F, Dong D, et al. Role of regulatory B cells in the progression of cervical cancer. Mediat Inflamm. 2019;2019:1–8.

    Google Scholar 

  32. Zegallai HM, Abu-El-Rub E, Mejia EM, Sparagna GC, Cole LK, Marshall AJ, et al. Tafazzin deficiency attenuates anti-cluster of differentiation 40 and interleukin-4 activation of mouse B lymphocytes. Cell Tissue Res. 2022. https://doi.org/10.1007/s00441-022-03692-z.

    Article  PubMed  Google Scholar 

  33. Tan R, Nie M, Long W. The role of B cells in cancer development. Front Oncol. 2022;12: 958756.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sarvaria A, Madrigal JA, Saudemont A. B cell regulation in cancer and anti-tumor immunity. Cell Mol Immunol. 2017;14(8):662–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nielsen JS, Sahota RA, Milne K, Kost SE, Nesslinger NJ, Watson PH, et al. CD20+ tumor-infiltrating lymphocytes have an atypical CD27− memory phenotype and together with CD8+ T-cells promote favorable prognosis in ovarian cancer. Clin Cancer Res. 2012;18(12):3281–92.

    Article  CAS  PubMed  Google Scholar 

  36. Katsnelson A. Kicking off adaptive immunity: the discovery of dendritic cells. J Exp Med. 2006;203(7):1622.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Wculek SK, Cueto FJ, Mujal AM, Melero I, Krummel MF, Sancho D. Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 2020;20:7–24.

    Article  CAS  PubMed  Google Scholar 

  38. Wylie B, Macri C, Mintern JD, Waithman J. Dendritic cells and cancer: from biology to therapeutic intervention. Cancers (Basel). 2019;11(4):521.

    Article  CAS  PubMed  Google Scholar 

  39. Freudenthal PS, Steinman RM. The distinct surface of human blood dendritic cells, as observed after an improved isolation method. Proc Natl Acad Sci. 1990;87(19):7698–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Anguille S, Smits EL, Lion E, van Tendeloo VF, Berneman ZN. Clinical use of dendritic cells for cancer therapy. Lancet Oncol. 2014;15(7):e257–67.

    Article  CAS  PubMed  Google Scholar 

  41. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev. 2008;224:166–82.

    Article  CAS  PubMed  Google Scholar 

  43. Gou Q, Dong C, Xu H, Khan B, Jin J, Liu Q, et al. PD-L1 degradation pathway and immunotherapy for cancer. Cell Death Dis. 2020;11(11):955.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Pentcheva-Hoang T, Egen JG, Wojnoonski K, Allison JP. B7–1 and B7–2 selectively recruit CTLA-4 and CD28 to the immunological synapse. Immunity. 2004;21(3):401–13.

    Article  CAS  PubMed  Google Scholar 

  45. Shiravand Y, Khodadadi F, Kashani SMA, Hosseini-Fard SR, Hosseini S, Sadeghirad H, et al. Immune checkpoint inhibitors in cancer therapy. Curr Oncol. 2022;29(5):3044–60.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Bellmunt J, De Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017;376(11):1015–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hodi FS, Mihm MC, Soiffer RJ, Haluska FG, Butler M, Seiden MV, et al. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci USA. 2003;100(8):4712–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Boyiadzis MM, Kirkwood JM, Marshall JL, Pritchard CC, Azad NS, Gulley JL. Significance and implications of FDA approval of pembrolizumab for biomarker-defined disease. J Immunother Cancer. 2018;6(1):35.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Santin AD, Deng W, Frumovitz M, Buza N, Bellone S, Huh W, et al. Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002). Gynecol Oncol. 2020;157(1):161–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Makker V, Taylor MH, Aghajanian C, Oaknin A, Mier J, Cohn AL, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer. J Clin Oncol. 2020;38(26):2981.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Guo Z, Cheng D, Xia Z, Luan M, Wu L, Wang G, et al. Combined TIM-3 blockade and CD137 activation affords the long-term protection in a murine model of ovarian cancer. J Transl Med. 2013;11(1):1–11.

    Article  Google Scholar 

  52. Wu B, Zhong C, Lang Q, Liang Z, Zhang Y, Zhao X, et al. Poliovirus receptor (PVR)-like protein cosignaling network: new opportunities for cancer immunotherapy. J Exp Clin Cancer Res. 2021;40(1):1–16.

    Article  CAS  Google Scholar 

  53. Smith M, Lara OD, O’Cearbhaill R, Knisely A, McEachron J, Gabor L, et al. Inflammatory markers in gynecologic oncology patients hospitalized with COVID-19 infection. Gynecol Oncol. 2020;159(3):618–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Li J, Cao C, Xiang Y, Hong Z, He D, Zhong H, et al. TLT2 suppresses Th1 response by promoting IL-6 production in monocyte through JAK/STAT3 signal pathway in tuberculosis. Front Immunol. 2020;11:2031.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Lee JB, Ha S-J, Kim HR. Clinical insights into novel immune checkpoint inhibitors. Front Pharmacol. 2021. https://doi.org/10.3389/fphar.2021.681320.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Anderson K, Eskander RN. Immune checkpoint inhibition in the treatment of gynecologic cancer. Curr Obstet Gynecol Rep. 2018;7(1):6–19.

    Article  Google Scholar 

  57. Barani M, Bilal M, Sabir F, Rahdar A, Kyzas GZ. Nanotechnology in ovarian cancer: diagnosis and treatment. Life Sci. 2021;266: 118914.

    Article  CAS  PubMed  Google Scholar 

  58. Bojadzic D, Chen J, Alcazar O, Buchwald P. Design, synthesis, and evaluation of novel immunomodulatory small molecules targeting the CD40–CD154 costimulatory protein-protein interaction. Molecules. 2018;23(5):1153.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Heong V, Ngoi N, Tan DSP. Update on immune checkpoint inhibitors in gynecological cancers. J Gynecol Oncol. 2017. https://doi.org/10.3802/jgo.2017.28.e20.

    Article  PubMed  Google Scholar 

  60. Solinas C, Migliori E, De Silva P, Willard-Gallo K. LAG3: the biological processes that motivate targeting this immune checkpoint molecule in human cancer. Cancers. 2019;11(8):1213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Goode EL, Block MS, Kalli KR, Vierkant RA, Chen W, Fogarty ZC, et al. Dose-response association of CD8+ tumor-infiltrating lymphocytes and survival time in high-grade serous ovarian cancer. JAMA Oncol. 2017;3(12): e173290.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Son J, George GC, Nardo M, Krause KJ, Jazaeri AA, Biter AB, et al. Adoptive cell therapy in gynaecologic cancers: a systematic review and meta-analysis. Gynecol Oncol. 2022;165(3):664–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Wu JWY, Dand S, Doig L, Papenfuss AT, Scott CL, Ho G, et al. T-Cell receptor therapy in the treatment of ovarian cancer: a mini review. Front Immunol. 2021;12: 672502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Zhu Y, Zhou J, Zhu L, Hu W, Liu B, Xie L. Adoptive tumor infiltrating lymphocytes cell therapy for cervical cancer. Hum Vaccin Immunother. 2022;18:5.

    Article  Google Scholar 

  65. Zhao L, Cao YJ. Engineered T cell therapy for cancer in the clinic. Front Immunol. 2019;10:2250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Morotti M, Albukhari A, Alsaadi A, Artibani M, Brenton JD, Curbishley SM, et al. Promises and challenges of adoptive T-cell therapies for solid tumours. Br J Cancer. 2021;124(11):1759–76.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. N Engl J Med. 1988;319(25):1676–80.

    Article  CAS  PubMed  Google Scholar 

  68. Kazemi MH, Sadri M, Najafi A, Rahimi A, Baghernejadan Z, Khorramdelazad H, et al. Tumor-infiltrating lymphocytes for treatment of solid tumors: it takes two to tango? Front Immunol. 2022;13:1018962.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Wallen H, Thompson JA, Reilly JZ, Rodmyre RM, Cao J, Yee C. Fludarabine modulates immune response and extends in vivo survival of adoptively transferred CD8 T cells in patients with metastatic melanoma. PLoS ONE. 2009;4(3): e4749.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008;26(32):5233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Howlader N, Noone A, Krapcho M, Miller D, Brest A, Yu M, et al. SEER Cancer Statistics Review, 1975–2016, National Cancer Institute. Bethesda, MD National Cancer Institute Bethesda, MD; 2019.

  73. Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(9):1274–84.

    Article  CAS  PubMed  Google Scholar 

  74. Barber A, Zhang T, Sentman CL. Immunotherapy with chimeric NKG2D receptors leads to long-term tumor-free survival and development of host antitumor immunity in murine ovarian cancer. J Immunol. 2008;180(1):72–8.

    Article  CAS  PubMed  Google Scholar 

  75. Liu H, Wang S, Xin J, Wang J, Yao C, Zhang Z. Role of NKG2D and its ligands in cancer immunotherapy. Am J Cancer Res. 2019;9(10):2064–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Serritella AV, Saenz-Lopez P, Dhar P, Liu S, Wu J. The clinical impact of soluble natural killer cell group 2-member D (NKG2D) receptor ligands on tumor tumorigenicity and anti-tumor immunity. J Clin Oncol. 2023;41(16):e14557.

    Article  Google Scholar 

  77. Uppendahl LD, Dahl CM, Miller JS, Felices M, Geller MA. Natural killer cell-based immunotherapy in gynecologic malignancy: a review. Front Immunol. 2018;8:1825.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Wright SE, Rewers-Felkins KA, Quinlin IS, Phillips CA, Townsend M, Philip R, et al. Cytotoxic T-lymphocyte immunotherapy for ovarian cancer: a pilot study. J Immunother (Hagerstown). 2012;35(2):196.

    Article  CAS  Google Scholar 

  79. Matsuzaki J, Gnjatic S, Mhawech-Fauceglia P, Beck A, Miller A, Tsuji T, et al. Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proc Natl Acad Sci USA. 2010;107(17):7875–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Qin R, Ren W, Ya G, Wang B, He J, Ren S, et al. Role of chemokines in the crosstalk between tumor and tumor-associated macrophages. Clin Exp Med. 2022. https://doi.org/10.1007/s10238-022-00888-z.

    Article  PubMed  PubMed Central  Google Scholar 

  81. De Jong R, Leffers N, Boezen H, ten Hoor KA, van der Zee AG, Hollema H, et al. Presence of tumor-infiltrating lymphocytes is an independent prognostic factor in type I and II endometrial cancer. Gynecol Oncol. 2009;114(1):105–10.

    Article  PubMed  Google Scholar 

  82. Ott PA, Bang YJ, Berton-Rigaud D, Elez E, Pishvaian MJ, Rugo HS, et al. Safety and antitumor activity of pembrolizumab in advanced programmed death ligand 1-positiveendometrial cancer: results from the KEYNOTE-028 study. J ClinOncol. 2017;35(22):2535–41.

    Article  CAS  Google Scholar 

  83. Marcus L, Lemery SJ, Keegan P, Pazdur R. FDA approval summary: pembrolizumab for the treatment of microsatellite instability-high solid tumors. Clin Cancer Res. 2019;25(13):3753–8.

    Article  CAS  PubMed  Google Scholar 

  84. Bonneville R, Krook MA, Chen HZ, Smith A, Samorodnitsky E, Wing MR, et al. Detection of microsatellite instability biomarkers via next-generation sequencing. Methods Mol Biol. 2020;2055:119–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Li K, Luo H, Huang L, Luo H, Zhu X. Microsatellite instability: a review of what the oncologist should know. Cancer Cell Int. 2020;20:16.

    Article  PubMed  PubMed Central  Google Scholar 

  86. Lower SS, McGurk MP, Clark AG, Barbash DA. Satellite DNA evolution: old ideas, new approaches. Curr Opin Genet Dev. 2018;49:70–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Makker V, Rasco D, Vogelzang NJ, Brose MS, Cohn AL, Mier J, et al. Lenvatinib plus pembrolizumabin patients with advanced endometrial cancer: an interim analysis of amulticentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019;20(5):711–8.

    Article  CAS  PubMed  Google Scholar 

  88. Santin A, Hermonat P, Ravaggi A, Bellone S, Cowan C, Coke C, et al. Development and therapeutic effect of adoptively transferred T cells primed by tumor lysate-pulsed autologous dendritic cells in a patient with metastatic endometrial cancer. Gynecol Obstet Invest. 2000;49(3):194–203.

    Article  CAS  PubMed  Google Scholar 

  89. Oaknin A, Gilbert L, Tinker AV, Brown J, Mathews C, Press J, et al. Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. J Immunother Cancer. 2022;10(1):e003777.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Oaknin A, Duska L, Sullivan R, Pothuri B. Preliminary safety, efficacy, and pharmacokinetic/pharmacodynamic characterization from GARNET, a phase I/II clinical trial of the anti–PD-1 monoclonal antibody, TSR-042, in patients with recurrent or advanced MSI-h and MSS endometrial cancer. Gynecol Oncol. 2019;154:17.

    Article  Google Scholar 

  91. Doran SL, Stevanović S, Adhikary S, Gartner JJ, Jia L, Kwong MLM, et al. T-cell receptor gene therapy for human papillomavirus-associated epithelial cancers: a first-in-human, phase I/II study. J Clin Oncol. 2019;37(30):2759–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Ge Y, Zhang Y, Zhao KN. Emerging therapeutic strategies of different immunotherapy approaches combined with PD-1/PD-L1 blockade in cervical cancer. Drug Des Devel Ther. 2022;16:3055–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Mazzotti L, Gaimari A, Bravaccini S, Maltoni R, Cerchione C, Juan M. T-cell receptor repertoire sequencing and its applications: focus on infectious diseases and cancer. Int J Mol Sci. 2022;23(15):8590.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Bryson P, Jia Q, Chen G, Li S, Fang J, Zhao L, et al. 1227p-HPV16 E6-SpecificTCR-T armored with checkpoint blockade in the treatment of cervical cancer. J Immunother Cancer. 2019;30: v502.

    Google Scholar 

  95. Litwin TR, Irvin SR, Chornock RL, Sahasrabuddhe VV, Stanley M, Wentzensen N. Infiltrating T-cell markers in cervical carcinogenesis: a systematic review and meta-analysis. Br J Cancer. 2021;124(4):831–41.

    Article  CAS  PubMed  Google Scholar 

  96. Yu L, Lanqing G, Huang Z, Xin X, Minglin L, Fa-hui L, et al. T cell immunotherapy for cervical cancer: challenges and opportunities. Front Immunol. 2023;14:1105265.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. He Y, Li X, Yin C, Wu YM. Killing cervical cancer cells by specific ChimeriAntigen receptor-modified T cells. J Reprod Immunol. 2020;139: 103115.

    Article  CAS  PubMed  Google Scholar 

  98. Zhang Y, Li X, Zhang J, Mao L. Novel cellular immunotherapy UsingNKG2D CAR-T for the treatment of cervical cancer. Bio Med Pharmacother. 2020;131: 110562.

    Article  CAS  Google Scholar 

  99. Xu Y, Jiang J, Wang Y, Wang W, Li H, Lai W, et al. Engineered T cell therapy for gynecologic malignancies: challenges and opportunities. Front Immunol. 2021;12: 725330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Oaknin A, Tinker AV, Gilbert L, Samouëlian V, Mathews C, Brown J, et al. Clinical activity and safety of the anti-PD-1 monoclonal antibody dostarlimab for patients with recurrent or advanced dMMR endometrial cancer. Future Oncol. 2021;17:3781–5.

    Article  CAS  PubMed  Google Scholar 

  101. Broderick JM. FDA Grants LN-145 Breakthrough Designation for Cervical Cancer. 2019. https://www.onclive.com/view/fda-grants-ln145-breakthrough-designation-for-cervical-cancerAccessed 20 Dec 2020.

  102. Kerkar SP, Wang Z, Lasota J, Park T, Patel K, Groh E, et al. MAGE-A is more highly expressed than NY-ESO-1 in a systematic immunohistochemical analysis of 3668 cases. J Immunother. 2016;39:181–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Rodriguez-Garcia A, Sharma P, Poussin M, Boesteanu AC, Minutolo NG, Gitto SB, et al. CAR T cells targeting MISIIR for the treatment of ovarian cancer and other gynecologic malignancies. Mol Ther. 2020;28:548–60.

    Article  CAS  PubMed  Google Scholar 

  104. Tanyi JL, Bobisse S, Ophir E, Tuyaerts S, Roberti A, Genolet R, et al. Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer. Sci Transl Med. 2018;10(436):eaao5931.

    Article  PubMed  Google Scholar 

  105. Chiang CL, Kandalaft LE, Tanyi J, Hagemann AR, Motz GT, Svoronos N, et al. A dendritic cell vaccine pulsed with autologous hypochlorous acid-oxidized ovarian cancer lysate primes effective broad antitumor immunity: from bench to bedside. Clin Cancer Res. 2013;19:4801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Fader AN, Diaz LA, Armstrong DK, Tanner EJ, Uram JN, Eyring A, et al. Preliminary results of a phase II study: PD-1 blockade in mismatch repair–deficient, recurrent or persistent endometrial cancer. Gynaecol Oncol. 2016;141:206–7.

    Article  Google Scholar 

  107. Yang C, Lee H, Jove V, Deng J, Zhang W, Liu X, et al. Prognostic significance of B-cells and pSTAT3 in patients with ovarian cancer. PLoS ONE. 2013;8(1): e54029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Wouters MC, Nelson BH. Prognostic significance of tumor-infiltrating B-cells and plasma cells in human cancer. Clin Cancer Res. 2018;24(24):6125–35.

    Article  CAS  PubMed  Google Scholar 

  109. Lundgren S, Berntsson J, Nodin B, Micke P, Jirström K. Prognostic impact of tumour-associated B-cells and plasma cells in epithelial ovarian cancer. J Ovarian Res. 2016;9(1):1–9.

    Article  Google Scholar 

  110. Gupta P, Chen C, Chaluvally-Raghavan P, Pradeep S. B-cells as an immune-regulatory signature in ovarian cancer. Cancers. 2019;11(7):894.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Biagi E, Rousseau R, Yvon E, Schwartz M, Dotti G, Foster A. Responses to human CD40 ligand/human interleukin-2 autologous cell vaccine in patients with B cell chronic lymphocytic leukemia. Clin Cancer Res. 2005;11(19):6916–23.

    Article  CAS  PubMed  Google Scholar 

  112. Kugler A, Seseke F, Thelen P, Kallerhoff M, Müller GA, Stuhler G, et al. Autologous and allogenic hybrid cell vaccine in patients with metastatic renal cell carcinoma. Br J Urol. 1998;82(4):487–93.

    Article  CAS  PubMed  Google Scholar 

  113. Trefzer U, Weingart G, Chen Y, Herberth G, Adrian K, Winter H, et al. Hybrid cell vaccination for cancer immune therapy: first clinical trial with metastatic melanoma. Int J Cancer. 2000;85(5):618–26.

    Article  CAS  PubMed  Google Scholar 

  114. Mandal G, Biswas S, Anadon CM, Yu X, Gatenbee CD, Prabhakaran S, et al. IgA-dominated humoral immune responses govern patients’ outcome in endometrial cancer. Cancer Res. 2021. https://doi.org/10.1158/0008-5472.CAN-21-2376.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Dzopalic T, Rajkovic I, Dragicevic A, Colic M. The response of human dendritic cells to co-ligation of pattern-recognition receptors. Immunol Res. 2012;52:20–33.

    Article  CAS  PubMed  Google Scholar 

  116. Murthy V, Moiyadi A, Sawant R, Sarin R. Clinical considerations in developing dendritic cell vaccine-based immunotherapy protocols in cancer. Curr Mol Med. 2009;9:725–31.

    Article  CAS  PubMed  Google Scholar 

  117. Brossart P, Wirths S, Stuhler G, Reichardt VL, Kanz L, Brugger W. Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood. 2000;96:3102–8.

    Article  CAS  PubMed  Google Scholar 

  118. Bhargava A, Srivastava RK, Mishra DK, Tiwari RR, Sharma RS, Mishra PK. Dendritic cell engineering for selective targeting of female reproductive tract cancers. Indian J Med Res. 2018;148(Suppl):S50–63.

    PubMed  PubMed Central  Google Scholar 

  119. Chen B, Liu L, Xu H, Yang Y, Zhang L, Zhang F. Effectiveness of immune therapy combined with chemotherapy on the immune function and recurrence rate of cervical cancer. Exp Ther Med. 2015;9:1063–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Coosemans A, Vanderstraeten A, Tuyaerts S, Verschuere T, Moerman P, Berneman Z, et al. Immunological response after WT1 mRNA-loaded dendritic cell immunotherapy in ovarian carcinoma and carcinosarcoma. Anticancer Res. 2013;33:3855–9.

    CAS  PubMed  Google Scholar 

  121. Gray H, Benigno B, Berek J, Chang J, Mason J, Mileshkin L, et al. Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial. J Immunother Cancer. 2016;4(1):34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Jiang L, Liu G, Ni W, Zhang N, Jie J, Xie F, et al. The combination of MBP and BCG-induced dendritic cell maturation through TLR2/TLR4 promotes Th1 activation in vitro and vivo. Mediat Inflamm. 2017;2017:1–14.

    Google Scholar 

  123. Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol. 2013;31:563–604.

    Article  CAS  PubMed  Google Scholar 

  124. Goyvaerts C, Breckpot K. The journey of in vivo virus engineered dendritic cells from bench to bedside: a bumpy road. Front Immunol. 2018. https://doi.org/10.3389/fimmu.2018.02052.

    Article  PubMed  PubMed Central  Google Scholar 

  125. Moyer TJ, Zmolek AC, Irvine DJ. Beyond antigens and adjuvants: formulating future vaccines. J Clin Investig. 2016;126(3):799–808.

    Article  PubMed  PubMed Central  Google Scholar 

  126. Idoyaga J, Lubkin A, Fiorese C, Lahoud MH, Caminschi I, Huang Y, et al. Comparable T helper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A. Proc Natl Acad Sci. 2011;108(6):2384–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Birkholz K, Schwenkert M, Kellner C, Gross S, Fey G, Schuler-Thurner B, et al. Targeting of DEC-205 on human dendritic cells results in efficient MHC class II–restricted antigen presentation. Blood J Am Soc Hematol. 2010;116(13):2277–85.

    CAS  Google Scholar 

  128. Mastelic-Gavillet B, Balint K, Boudousquie C, Gannon PO, Kandalaft LE. Personalized dendritic cell vaccines—recent breakthroughs and encouraging clinical results. Front Immunol. 2019;10:766.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Roddie C, O’Reilly M, Dias Alves Pinto J, Vispute K, Lowdell M. Manufacturing chimeric antigen receptor T cells: issues and challenges. Cytotherapy. 2019;21:327–40.

    Article  CAS  PubMed  Google Scholar 

  130. Depil S, Duchateau P, Grupp SA, Mufti G, Poirot L. ‘Off- the-shelf’ allogeneic CAR T cells: development and challenges. Nat Rev Drug Discov. 2020;19:185–99.

    Article  CAS  PubMed  Google Scholar 

  131. Ren J, Liu X, Fang C, Jiang S, June CH, Zhao Y. Multiplex genome editing togenerate universal CAR T cells resistant to PD1 inhibition. Clin Cancer Res. 2017;23:2255–66.

    Article  CAS  PubMed  Google Scholar 

  132. Lund FE, Randall TD. Effector and regulatory B-cells: modulators of CD4+ T-cell immunity. Nat Rev Immunol. 2010;10(4):236–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Irvine DJ, Maus MV, Mooney DJ, Wong WW. The future of engineered immune cell therapies. Science. 2022;378(6622):853–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Al-Shibli KI, Donnem T, Al-Saad S, Persson M, Bremnes RM, Busund LT. Prognostic effect of epithelial and stromal lymphocyte infiltration in non–small cell lung cancer. Clin Cancer Res. 2008;14(16):5220–7.

    Article  CAS  PubMed  Google Scholar 

  135. Nedergaard BS, Ladekarl M, Nyengaard JR, Nielsen K. A comparative study of the cellular immune response in patients with stage IB cervical squamous cell carcinoma. Low numbers of several immune cell subtypes are strongly associated with relapse of disease within 5 years. Gynecol Oncol. 2008;108(1):106–11.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are highly grateful to the NSHM Knowledge Campus, Kolkata, Maulana Abul Kalam Azad University of Technology, Jadavpur University and Chittaranjan National Cancer Institute, Kolkata for their continuous support.

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Maulana Abul Kalam Azad University of Technology, Kolkata, West Bengal, India

    Sandipan Dasgupta

  2. NSHM Knowledge Campus, Kolkata - Group of Institutions, 124, B. L. Saha Road, Tara Park, Behala, Kolkata, West Bengal, 700053, India

    Sakuntala Gayen, Tania Chakraborty & Souvik Roy

  3. Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India

    Naureen Afrose

  4. Department of Pathology and Cancer Screening, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India

    Ranita Pal, Sutapa Mahata & Vilas Nasare

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SD, SG, TC, NA, RP, and SM participated in data collection and manuscript writing. SD and VN drafted and SR revised the final manuscript. All authors have fully read and approved the final manuscript.

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Dasgupta, S., Gayen, S., Chakraborty, T. et al. Potential role of immune cell therapy in gynecological cancer and future promises: a comprehensive review. Med Oncol 41, 98 (2024). https://doi.org/10.1007/s12032-024-02337-1

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