Recent Developments in Combinatorial Immunotherapy towards Ovarian
Cancer

Chakresh   Kumar   Jain; Aishani      Kulshreshtha; Harshita      Saxena; Avinav      Agarwal; Kalpdrum      Passi
Abstract

Ovarian cancer is one of the most common cancers in women in the world. It is also the 5th top cause of cancer-related death in the world. Despite chemotherapy being the primary treatment along with surgery, patients frequently suffer from a recurrence of ovarian cancer within a few years of the original treatment. The recurring nature of OC, therefore, necessitates the development of novel therapeutic interventions that can effectively tackle this disease. Immunotherapy has lately been found to offer significant clinical advantages. Some of the immunotherapy techniques being studied for ovarian cancer include adoptive T-cell treatment, immune checkpoint inhibition, and oncolytic virus. However, the most efficient way to increase longevity is through a combination of immunotherapy strategies with other disease therapeutic approaches such as radiotherapy, chemotherapy, and PARPi in additive or synergistic ways. To provide a more comprehensive insight into the current immunotherapies explored, this paper explores newly developed therapeutics for the disease with an emphasis on current outstanding immunotherapy. The current state of our understanding of how the disease interacts with host cells, current therapy options available, various advanced treatments present and the potential for combinatorial immuno-based therapies in the future have also been explored.
Graphical Abstract

[1]
Swerdlow, M. Mesothelioma of the pelvic peritoneum resembling papillary cystadenocarcinoma of the ovary. Am. J. Obstet. Gynecol.,  1959, 77(1), 197-200.
 [http://dx.doi.org/10.1016/0002-9378(59)90287-X] [PMID: 13606191]

[2]
 American Cancer Society. Key Statistics for Ovarian Cancer. Available from: https://www.cancer.org/cancer/ovarian-cancer/about/key-statistics.html

[3]
Miller, K.D.; Nogueira, L.; Mariotto, A.B.; Rowland, J.H.; Yabroff, K.R.; Alfano, C.M.; Jemal, A.; Kramer, J.L.; Siegel, R.L. Cancer treatment and survivorship statistics, 2019. CA Cancer J. Clin.,  2019, 69(5), 363-385.
 [http://dx.doi.org/10.3322/caac.21565] [PMID: 31184787]

[4]
Chandra, A.; Pius, C.; Nabeel, M.; Nair, M.; Vishwanatha, J.K.; Ahmad, S.; Basha, R. Ovarian cancer: Current status and strategies for improving therapeutic outcomes. Cancer Med.,  2019, 8(16), 7018-7031.
 [http://dx.doi.org/10.1002/cam4.2560] [PMID: 31560828]

[5]
Matulonis, U.A.; Sood, A.K.; Fallowfield, L.; Howitt, B.E.; Sehouli, J.; Karlan, B.Y. Ovarian cancer. Nat. Rev. Dis. Primers,  2016, 2(1), 16061.
 [http://dx.doi.org/10.1038/nrdp.2016.61] [PMID: 27558151]

[6]
Corrado, G.; Salutari, V.; Palluzzi, E.; Distefano, M.G.; Scambia, G.; Ferrandina, G. Optimizing treatment in recurrent epithelial ovarian cancer. Expert Rev. Anticancer Ther.,  2017, 17(12), 1147-1158.
 [http://dx.doi.org/10.1080/14737140.2017.1398088] [PMID: 29086618]

[7]
Mittica, G.; Ghisoni, E.; Giannone, G.; Genta, S.; Aglietta, M.; Sapino, A.; Valabrega, G. PARP inhibitors in ovarian cancer. Recent Patents Anticancer Drug Discov.,  2018, 13(4), 392-410.
 [http://dx.doi.org/10.2174/1574892813666180305165256] [PMID: 29512470]

[8]
Tan, S.; Li, D.; Zhu, X. Cancer immunotherapy: Pros, cons and beyond. Biomed. Pharmacother.,  2020, 124, 109821.
 [http://dx.doi.org/10.1016/j.biopha.2020.109821] [PMID: 31962285]

[9]
Yang, S.; Yin, X.; Yue, Y.; Wang, S. Application of adoptive immunotherapy in ovarian cancer. OncoTargets Ther.,  2019, 12, 7975-7991.
 [http://dx.doi.org/10.2147/OTT.S221773] [PMID: 31632055]

[10]
Nwani, N.; Sima, L.; Nieves-Neira, W.; Matei, D. Targeting the microenvironment in high grade serous ovarian cancer. Cancers,  2018, 10(8), 266.
 [http://dx.doi.org/10.3390/cancers10080266] [PMID: 30103384]

[11]
Baci, D.; Bosi, A.; Gallazzi, M.; Rizzi, M.; Noonan, D.M.; Poggi, A.; Bruno, A.; Mortara, L. The Ovarian Cancer Tumor Immune Microenvironment (TIME) as target for therapy: A focus on innate immunity cells as therapeutic effectors. Int. J. Mol. Sci.,  2020, 21(9), 3125.
 [http://dx.doi.org/10.3390/ijms21093125] [PMID: 32354198]

[12]
Liu, J.; Geng, X.; Li, Y. Milky spots: Omental functional units and hotbeds for peritoneal cancer metastasis. Tumour Biol.,  2016, 37(5), 5715-5726.
 [http://dx.doi.org/10.1007/s13277-016-4887-3] [PMID: 26831659]

[13]
Olalekan, S.; Xie, B.; Back, R.; Eckart, H.; Basu, A. Characterizing the tumor microenvironment of metastatic ovarian cancer by single-cell transcriptomics. Cell Rep.,  2021, 35(8), 109165.
 [http://dx.doi.org/10.1016/j.celrep.2021.109165] [PMID: 34038734]

[14]
Freedman, R.S.; Deavers, M.; Liu, J.; Wang, E. Peritoneal inflammation-a microenvironment for Epithelial Ovarian Cancer (EOC). J. Transl. Med.,  2004, 2(1), 23.
 [http://dx.doi.org/10.1186/1479-5876-2-23] [PMID: 15219235]

[15]
Eckert, M.A.; Orozco, C.; Xiao, J.; Javellana, M.; Lengyel, E. The effects of chemotherapeutics on the ovarian cancer microenvironment. Cancers,  2021, 13(13), 3136.
 [http://dx.doi.org/10.3390/cancers13133136] [PMID: 34201616]

[16]
Nersesian, S.; Glazebrook, H.; Toulany, J.; Grantham, S.R.; Boudreau, J.E. Naturally killing the silent killer: NK cell-based immunotherapy for ovarian cancer. Front. Immunol.,  2019, 10, 1782.
 [http://dx.doi.org/10.3389/fimmu.2019.01782] [PMID: 31456796]

[17]
Macpherson, A.M.; Barry, S.C.; Ricciardelli, C.; Oehler, M.K. Epithelial ovarian cancer and the immune system: Biology, interactions, challenges and potential advances for immunotherapy. J. Clin. Med.,  2020, 9(9), 2967.
 [http://dx.doi.org/10.3390/jcm9092967] [PMID: 32937961]

[18]
Worzfeld, T.; Pogge von Strandmann, E.; Huber, M.; Adhikary, T.; Wagner, U.; Reinartz, S.; Müller, R. The unique molecular and cellular microenvironment of ovarian cancer. Front. Oncol.,  2017, 7, 24.
 [http://dx.doi.org/10.3389/fonc.2017.00024] [PMID: 28275576]

[19]
Mantovani, A.; Marchesi, F.; Malesci, A.; Laghi, L.; Allavena, P. Tumour-associated macrophages as treatment targets in oncology. Nat. Rev. Clin. Oncol.,  2017, 14(7), 399-416.
 [http://dx.doi.org/10.1038/nrclinonc.2016.217] [PMID: 28117416]

[20]
Steinhart, B.; Jordan, K.R.; Bapat, J.; Post, M.D.; Brubaker, L.W.; Bitler, B.G.; Wrobel, J. The spatial context of tumor-infiltrating immune cells associates with improved ovarian cancer survival. Mol. Cancer Res.,  2021, 19(12), 1973-1979.
 [http://dx.doi.org/10.1158/1541-7786.MCR-21-0411] [PMID: 34615692]

[21]
Giraldo, N.A.; Sanchez-Salas, R.; Peske, J.D.; Vano, Y.; Becht, E.; Petitprez, F.; Validire, P.; Ingels, A.; Cathelineau, X.; Fridman, W.H.; Sautès-Fridman, C. The clinical role of the TME in solid cancer. Br. J. Cancer,  2019, 120(1), 45-53.
 [http://dx.doi.org/10.1038/s41416-018-0327-z] [PMID: 30413828]

[22]
Takahashi, H.; Sakakura, K.; Kudo, T.; Toyoda, M.; Kaira, K.; Oyama, T.; Chikamatsu, K. Cancer-associated fibroblasts promote an immunosuppressive microenvironment through the induction and accumulation of protumoral macrophages. Oncotarget,  2017, 8(5), 8633-8647.
 [http://dx.doi.org/10.18632/oncotarget.14374] [PMID: 28052009]

[23]
Ignacio, R.M.C.; Lee, E.S.; Wilson, A.J.; Beeghly-Fadiel, A.; Whalen, M.M.; Son, D.S. Chemokine network and overall survival in TP53 wild-type and mutant ovarian cancer. Immune Netw.,  2018, 18(4), e29.
 [http://dx.doi.org/10.4110/in.2018.18.e29] [PMID: 30181917]

[24]
Li, N.; Li, B.; Zhan, X. Comprehensive analysis of tumor microenvironment identified prognostic immune-related gene signature in ovarian cancer. Front. Genet.,  2021, 12, 616073.
 [http://dx.doi.org/10.3389/fgene.2021.616073] [PMID: 33679883]

[25]
Xie, B.; Tan, G.; Ren, J.; Lu, W.; Pervaz, S.; Ren, X.; Otoo, A.A.; Tang, J.; Li, F.; Wang, Y.; Wang, M. RB1 is an immune-related prognostic biomarker for ovarian cancer. Front. Oncol.,  2022, 12, 830908.
 [http://dx.doi.org/10.3389/fonc.2022.830908] [PMID: 35299734]

[26]
Jiang, S.; Yang, Y.; Zhang, Y.; Ye, Q.; Song, J.; Zheng, M.; Li, X. Overexpression of CAPG is associated with poor prognosis and immunosuppressive cell infiltration in ovarian cancer. Dis. Markers,  2022, 2022, 1-18.
 [http://dx.doi.org/10.1155/2022/9719671] [PMID: 35186171]

[27]
Yang, M.; Lu, J.; Zhang, G.; Wang, Y.; He, M.; Xu, Q.; Xu, C.; Liu, H. CXCL13 shapes immunoactive tumor microenvironment and enhances the efficacy of PD-1 checkpoint blockade in high-grade serous ovarian cancer. J. Immunother. Cancer,  2021, 9(1), e001136.
 [http://dx.doi.org/10.1136/jitc-2020-001136] [PMID: 33452206]

[28]
Wang, K.; Feng, X.; Zheng, L.; Chai, Z.; Yu, J.; You, X.; Li, X.; Cheng, X. TRPV4 is a prognostic biomarker that correlates with the immunosuppressive microenvironment and chemoresistance of anti-cancer drugs. Front. Mol. Biosci.,  2021, 8, 690500.
 [http://dx.doi.org/10.3389/fmolb.2021.690500] [PMID: 34262942]

[29]
Cortez, A.J.; Tudrej, P.; Kujawa, K.A.; Lisowska, K.M. Advances in ovarian cancer therapy. Cancer Chemother. Pharmacol.,  2018, 81(1), 17-38.
 [http://dx.doi.org/10.1007/s00280-017-3501-8] [PMID: 29249039]

[30]
Musella, A.; Vertechy, L.; Romito, A.; Marchetti, C.; Giannini, A.; Sciuga, V.; Bracchi, C.; Tomao, F.; Di Donato, V.; De Felice, F.; Monti, M.; Muzii, L.; Benedetti Panici, P. Bevacizumab in ovarian cancer: State of the art and unanswered questions. Chemotherapy,  2017, 62(2), 111-120.
 [http://dx.doi.org/10.1159/000448942] [PMID: 27794568]

[31]
Rutkowski, P.; Śpiewankiewicz, B.; Herman, K.; Jastrzębski, T.; Kładny, J.; Kojs, Z.; Krzakowski, M.; Polkowski, W.; Wyrwicz, L.; Wysocki, P.; Zdzienicki, M.; Zegarski, W. Polish clinical practice guideline on hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery in peritoneal malignancy treatment. Curr. Gynecologic Oncol,  2014, 12(2), 86-97.
 [http://dx.doi.org/10.15557/CGO.2014.0009]

[32]
Basta, A.; Bidziński, M.; Bieńkiewicz, A.; Blecharz, P.; Bodnar, L.; Jach, R.; Knapp, P.; Kojs, Z.; Kotarski, J.; Markowska, J.; Misiek, M.; Sznurkowski, J.; Wicherek, Ł.; Sawicki, W.; Timorek, A.; Bahyrycz, J.; Mądry, R. Recommendation of the polish society of oncological gynaecology on the diagnosis and treatment of epithelial ovarian cancer. Oncol. Clin. Pract.,  2015, 11(5), 233-243.

[33]
Urbański, K. Consolidation therapy of ovarian cancer. Oncol. Clin. Prac.,  2007, 3(6), 298-305.

[34]
Peng, M.; Mo, Y.; Wang, Y.; Wu, P.; Zhang, Y.; Xiong, F.; Guo, C.; Wu, X.; Li, Y.; Li, X.; Li, G.; Xiong, W.; Zeng, Z. Neoantigen vaccine: An emerging tumor immunotherapy. Mol. Cancer,  2019, 18(1), 128.
 [http://dx.doi.org/10.1186/s12943-019-1055-6] [PMID: 31443694]

[35]
Panici, B.P.; Giannini, A.; Fischetti, M.; Lecce, F.; Di Donato, V. Lymphadenectomy in ovarian cancer: Is it still justified? Curr. Oncol. Rep.,  2020, 22(3), 22.
 [http://dx.doi.org/10.1007/s11912-020-0883-2] [PMID: 32036457]

[36]
Zhang, Y.; Zhang, Z. The history and advances in cancer immunotherapy: Understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell. Mol. Immunol.,  2020, 17(8), 807-821.
 [http://dx.doi.org/10.1038/s41423-020-0488-6] [PMID: 32612154]

[37]
Johnson, R.L.; Cummings, M.; Thangavelu, A.; Theophilou, G.; de Jong, D.; Orsi, N.M. Barriers to immunotherapy in ovarian cancer: Metabolic, genomic, and immune perturbations in the tumour microenvironment. Cancers,  2021, 13(24), 6231.
 [http://dx.doi.org/10.3390/cancers13246231] [PMID: 34944851]

[38]
Brahmer, J.R.; Tykodi, S.S.; Chow, L.Q.M.; Hwu, W.J.; Topalian, S.L.; Hwu, P.; Drake, C.G.; Camacho, L.H.; Kauh, J.; Odunsi, K.; Pitot, H.C.; Hamid, O.; Bhatia, S.; Martins, R.; Eaton, K.; Chen, S.; Salay, T.M.; Alaparthy, S.; Grosso, J.F.; Korman, A.J.; Parker, S.M.; Agrawal, S.; Goldberg, S.M.; Pardoll, D.M.; Gupta, A.; Wigginton, J.M. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med.,  2012, 366(26), 2455-2465.
 [http://dx.doi.org/10.1056/NEJMoa1200694] [PMID: 22658128]

[39]
Leary, A.; Tan, D.; Ledermann, J. Immune checkpoint inhibitors in ovarian cancer: Where do we stand? Ther. Adv. Med. Oncol.,  2021, 13.
 [http://dx.doi.org/10.1177/17588359211039899] [PMID: 34422119]

[40]
Gou, Q.; Dong, C.; Xu, H.; Khan, B.; Jin, J.; Liu, Q.; Shi, J.; Hou, Y. PD-L1 degradation pathway and immunotherapy for cancer. Cell Death Dis.,  2020, 11(11), 955.
 [http://dx.doi.org/10.1038/s41419-020-03140-2] [PMID: 33159034]

[41]
Iwai, Y.; Hamanishi, J.; Chamoto, K.; Honjo, T. Cancer immunotherapies targeting the PD-1 signaling pathway. J. Biomed. Sci.,  2017, 24(1), 26.
 [http://dx.doi.org/10.1186/s12929-017-0329-9] [PMID: 28376884]

[42]
Moore, K.N.; Bookman, M.; Sehouli, J.; Miller, A.; Anderson, C.; Scambia, G.; Myers, T.; Taskiran, C.; Robison, K.; Mäenpää, J.; Willmott, L.; Colombo, N.; Thomes-Pepin, J.; Liontos, M.; Gold, M.A.; Garcia, Y.; Sharma, S.K.; Darus, C.J.; Aghajanian, C.; Okamoto, A.; Wu, X.; Safin, R.; Wu, F.; Molinero, L.; Maiya, V.; Khor, V.K.; Lin, Y.G.; Pignata, S. Atezolizumab, bevacizumab, and chemotherapy for newly diagnosed stage III or IV ovarian cancer: Placebo-controlled randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39). J. Clin. Oncol.,  2021, 39(17), 1842-1855.
 [http://dx.doi.org/10.1200/JCO.21.00306] [PMID: 33891472]

[43]
How, J.A.; Jazaeri, A.; Westin, S.N.; Sood, A.K.; Ramondetta, L.M.; Xu, M.; Abonofal, A.; Karp, D.D.; Subbiah, V.; Stephen, B.; Rodon, J.A.; Yang, F.; Naing, A. The clinical efficacy and safety of single-agent pembrolizumab in patients with recurrent granulosa cell tumors of the ovary: A case series from a phase II basket trial. Invest. New Drugs,  2021, 39(3), 829-835.
 [http://dx.doi.org/10.1007/s10637-020-01043-9] [PMID: 33415580]

[44]
Liao, J.B.; Gwin, W.R.; Urban, R.R.; Hitchcock-Bernhardt, K.M.; Coveler, A.L.; Higgins, D.M.; Childs, J.S.; Shakalia, H.N.; Swensen, R.E.; Stanton, S.E.; Tinker, A.V.; Wahl, T.A.; Ancheta, R.G.; McGonigle, K.F.; Dai, J.Y.; Disis, M.L.; Goff, B.A. Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: Survival and immune correlates. J. Immunother. Cancer,  2021, 9(9), e003122.
 [http://dx.doi.org/10.1136/jitc-2021-003122] [PMID: 34531249]

[45]
Natoli, M.; Bonito, N.; Robinson, J.D.; Ghaem-Maghami, S.; Mao, Y. Human ovarian cancer intrinsic mechanisms regulate lymphocyte activation in response to immune checkpoint blockade. Cancer Immunol. Immunother.,  2020, 69(8), 1391-1401.
 [http://dx.doi.org/10.1007/s00262-020-02544-5] [PMID: 32200422]

[46]
Silk, A.W.; Saraiya, B.; Groisberg, R.; Chan, N.; Spencer, K.; Girda, E.; Shih, W.; Palmeri, M.; Saunders, T.; Berman, R.M.; Coric, V.; Chen, S.; Zloza, A.; Vieth, J.; Mehnert, J.M.; Malhotra, J. A phase Ib dose-escalation study of troriluzole (BHV-4157), an oral glutamatergic signaling modulator, in combination with nivolumab in patients with advanced solid tumors. Eur. J. Med. Res.,  2022, 27(1), 107.
 [http://dx.doi.org/10.1186/s40001-022-00732-w] [PMID: 35780243]

[47]
 Chia Tai Tianqing Pharmaceutical Group Co., Ltd. A Multicenter, Randomized, Open, Parallel Controlled Phase III Clinical Trial to Evaluate the Efficacy and Safety of TQB2450 Injection Combined With Androtinib Hydrochloride Capsules Versus Paclitaxel as Weekly Treatment in the Treatment of Recurrent Platinumresistant Ovarian Cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT05145218

[48]
Xia, L.; Peng, J.; Lou, G.; Pan, M.; Zhou, Q.; Hu, W.; Shi, H.; Wang, L.; Gao, Y.; Zhu, J.; Zhang, Y.; Sun, R.; Zhou, X.; Wang, Q.; Wu, X. Antitumor activity and safety of camrelizumab plus famitinib in patients with platinum-resistant recurrent ovarian cancer: Results from an open-label, multicenter phase 2 basket study. J. Immunother. Cancer,  2022, 10(1), e003831.
 [http://dx.doi.org/10.1136/jitc-2021-003831] [PMID: 35017154]

[49]
Lee, J.Y.; Kim, B.G.; Kim, J.W.; Lee, J.B.; Park, E.; Joung, J.G.; Kim, S.; Choi, C.H.; Kim, H.S. Biomarker-guided targeted therapy in platinum-resistant ovarian cancer (AMBITION; KGOG 3045): a multicentre, open-label, five-arm, uncontrolled, umbrella trial. J. Gynecol. Oncol.,  2022, 33(4), e45.
 [http://dx.doi.org/10.3802/jgo.2022.33.e45] [PMID: 35320892]

[50]
Grobben, Y.; de Man, J.; van Doornmalen, A.M.; Muller, M.; Willemsen-Seegers, N.; Vu-Pham, D.; Mulder, W.R.; Prinsen, M.B.W.; de Wit, J.; Sterrenburg, J.G.; van Cauter, F.; den Ouden, J.E.; van Altena, A.M.; Massuger, L.F.; Uitdehaag, J.C.M.; Buijsman, R.C.; Zaman, G.J.R. Targeting indoleamine 2,3-Dioxygenase in cancer models using the novel small molecule inhibitor NTRC 3883-0. Front. Immunol.,  2021, 11, 609490.
 [http://dx.doi.org/10.3389/fimmu.2020.609490] [PMID: 33584686]

[51]
Yang, C.; Xia, B.R.; Zhang, Z.C.; Zhang, Y.J.; Lou, G.; Jin, W.L. Immunotherapy for ovarian cancer: Adjuvant, combination, and neoadjuvant. Front. Immunol.,  2020, 11, 577869.
 [http://dx.doi.org/10.3389/fimmu.2020.577869] [PMID: 33123161]

[52]
Rowshanravan, B.; Halliday, N.; Sansom, D.M. CTLA-4: A moving target in immunotherapy. Blood,  2018, 131(1), 58-67.
 [http://dx.doi.org/10.1182/blood-2017-06-741033] [PMID: 29118008]

[53]
Świderska, J.; Kozłowski, M.; Nowak, K.; Rychlicka, M.; Branecka-Woźniak, D.; Kwiatkowski, S.; Pius-Sadowska, E.; Machaliński, B.; Cymbaluk-Płoska, A. Clinical relevance of soluble forms of immune checkpoint molecules sPD-1, sPD-L1, and sCTLA-4 in the diagnosis and prognosis of ovarian cancer. Diagnostics,  2022, 12(1), 189.
 [http://dx.doi.org/10.3390/diagnostics12010189] [PMID: 35054356]

[54]
Tu, L.; Guan, R.; Yang, H.; Zhou, Y.; Hong, W.; Ma, L.; Zhao, G.; Yu, M. Assessment of the expression of the immune checkpoint molecules PD‐1, CTLA4, TIM‐3 and LAG‐3 across different cancers in relation to treatment response, tumor‐infiltrating immune cells and survival. Int. J. Cancer,  2020, 147(2), 423-439.
 [http://dx.doi.org/10.1002/ijc.32785] [PMID: 31721169]

[55]
Wan, C.; Keany, M.P.; Dong, H.; Al-Alem, L.F.; Pandya, U.M.; Lazo, S.; Boehnke, K.; Lynch, K.N.; Xu, R.; Zarrella, D.T.; Gu, S.; Cejas, P.; Lim, K.; Long, H.W.; Elias, K.M.; Horowitz, N.S.; Feltmate, C.M.; Muto, M.G.; Worley, M.J., Jr; Berkowitz, R.S.; Matulonis, U.A.; Nucci, M.R.; Crum, C.P.; Rueda, B.R.; Brown, M.; Liu, X.S.; Hill, S.J. Enhanced efficacy of simultaneous PD-1 and PD-L1 immune checkpoint blockade in high-grade serous ovarian cancer. Cancer Res.,  2021, 81(1), 158-173.
 [http://dx.doi.org/10.1158/0008-5472.CAN-20-1674] [PMID: 33158814]

[56]
Andrews, L.P.; Marciscano, A.E.; Drake, C.G.; Vignali, D.A.A. LAG3 (CD223) as a cancer immunotherapy target. Immunol. Rev.,  2017, 276(1), 80-96.
 [http://dx.doi.org/10.1111/imr.12519] [PMID: 28258692]

[57]
Das, M.; Zhu, C.; Kuchroo, V.K. Tim-3 and its role in regulating anti-tumor immunity. Immunol. Rev.,  2017, 276(1), 97-111.
 [http://dx.doi.org/10.1111/imr.12520] [PMID: 28258697]

[58]
Santoiemma, P.P.; Powell, D.J., Jr Tumor infiltrating lymphocytes in ovarian cancer. Cancer Biol. Ther.,  2015, 16(6), 807-820.
 [http://dx.doi.org/10.1080/15384047.2015.1040960] [PMID: 25894333]

[59]
Le Page, C.; Marineau, A.; Bonza, P.K.; Rahimi, K.; Cyr, L.; Labouba, I.; Madore, J.; Delvoye, N.; Mes-Masson, A.M.; Provencher, D.M.; Cailhier, J.F. BTN3A2 expression in epithelial ovarian cancer is associated with higher tumor infiltrating T cells and a better prognosis. PLoS One,  2012, 7(6), e38541.
 [http://dx.doi.org/10.1371/journal.pone.0038541] [PMID: 22685580]

[60]
Milne, K.; Köbel, M.; Kalloger, S.E.; Barnes, R.O.; Gao, D.; Gilks, C.B.; Watson, P.H.; Nelson, B.H. Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS One,  2009, 4(7), e6412.
 [http://dx.doi.org/10.1371/journal.pone.0006412] [PMID: 19641607]

[61]
Hao, J.; Yu, H.; Zhang, T.; An, R.; Xue, Y. Prognostic impact of tumor-infiltrating lymphocytes in high grade serous ovarian cancer: a systematic review and meta-analysis. Ther. Adv. Med. Oncol.,  2020, 12.
 [http://dx.doi.org/10.1177/1758835920967241] [PMID: 33193829]

[62]
Bobisse, S.; Genolet, R.; Roberti, A.; Tanyi, J.L.; Racle, J.; Stevenson, B.J.; Iseli, C.; Michel, A.; Le Bitoux, M.A.; Guillaume, P.; Schmidt, J.; Bianchi, V.; Dangaj, D.; Fenwick, C.; Derré, L.; Xenarios, I.; Michielin, O.; Romero, P.; Monos, D.S.; Zoete, V.; Gfeller, D.; Kandalaft, L.E.; Coukos, G.; Harari, A. Sensitive and frequent identification of high avidity neo-epitope specific CD8 + T cells in immunotherapy-naive ovarian cancer. Nat. Commun.,  2018, 9(1), 1092.
 [http://dx.doi.org/10.1038/s41467-018-03301-0] [PMID: 29545564]

[63]
Mittica, G.; Capellero, S.; Genta, S.; Cagnazzo, C.; Aglietta, M.; Sangiolo, D.; Valabrega, G. Adoptive immunotherapy against ovarian cancer. J. Ovarian Res.,  2016, 9(1), 30.
 [http://dx.doi.org/10.1186/s13048-016-0236-9] [PMID: 27188274]

[64]
Uppendahl, L.D.; Felices, M.; Bendzick, L.; Ryan, C.; Kodal, B.; Hinderlie, P.; Boylan, K.L.M.; Skubitz, A.P.N.; Miller, J.S.; Geller, M.A. Cytokine-induced memory-like natural killer cells have enhanced function, proliferation, and in vivo expansion against ovarian cancer cells. Gynecol. Oncol.,  2019, 153(1), 149-157.
 [http://dx.doi.org/10.1016/j.ygyno.2019.01.006] [PMID: 30658847]

[65]
Gonzalez, V.D.; Huang, Y.W.; Delgado-Gonzalez, A.; Chen, S.Y.; Donoso, K.; Sachs, K.; Gentles, A.J.; Allard, G.M.; Kolahi, K.S.; Howitt, B.E.; Porpiglia, E.; Fantl, W.J. High-grade serous ovarian tumor cells modulate NK cell function to create an immune-tolerant microenvironment. Cell Rep.,  2021, 36(9), 109632.
 [http://dx.doi.org/10.1016/j.celrep.2021.109632] [PMID: 34469729]

[66]
Li, Y.; Hermanson, D.L.; Moriarity, B.S.; Kaufman, D.S. Human iPSC-derived natural killer cells engineered with chimeric antigen receptors enhance anti-tumor activity. Cell Stem Cell,  2018, 23(2), 181-192.e5.
 [http://dx.doi.org/10.1016/j.stem.2018.06.002] [PMID: 30082067]

[67]
Jennings, V.A.; Ilett, E.J.; Scott, K.J.; West, E.J.; Vile, R.; Pandha, H.; Harrington, K.; Young, A.; Hall, G.D.; Coffey, M.; Selby, P.; Errington-Mais, F.; Melcher, A.A. Lymphokine‐activated killer and dendritic cell carriage enhances oncolytic reovirus therapy for ovarian cancer by overcoming antibody neutralization in ascites. Int. J. Cancer,  2014, 134(5), 1091-1101.
 [http://dx.doi.org/10.1002/ijc.28450] [PMID: 23982804]

[68]
Chen, C.; Lv, Y. The biological behavior of drug-resistantovarian cancer cells and changes in the CA125 and HE4 levels after CIK interventions. Am. J. Transl. Res.,  2021, 13(4), 2976-2982.
 [PMID: 34017464]

[69]
Qin, W.; Xiong, Y.; Chen, J.; Huang, Y.; Liu, T. DC‐CIK cells derived from ovarian cancer patient menstrual blood activate the TNFR1‐ASK1‐AIP1 pathway to kill autologous ovarian cancer stem cells. J. Cell. Mol. Med.,  2018, 22(7), 3364-3376.
 [http://dx.doi.org/10.1111/jcmm.13611] [PMID: 29566310]

[70]
Zhou, Y.; Chen, C.; Jiang, S.; Feng, Y.; Yuan, L.; Chen, P.; Zhang, L.; Huang, S.; Li, J.; Xia, J.C.; Zheng, M. Retrospective analysis of the efficacy of adjuvant CIK cell therapy in epithelial ovarian cancer patients who received postoperative chemotherapy. OncoImmunology,  2019, 8(2), e1528411.
 [http://dx.doi.org/10.1080/2162402X.2018.1528411] [PMID: 30713783]

[71]
Capellero, S.; Erriquez, J.; Melano, C.; Mesiano, G.; Genta, S.; Pisacane, A.; Mittica, G.; Ghisoni, E.; Olivero, M.; Di Renzo, M.F.; Aglietta, M.; Sangiolo, D.; Valabrega, G. Preclinical immunotherapy with Cytokine-Induced Killer lymphocytes against epithelial ovarian cancer. Sci. Rep.,  2020, 10(1), 6478.
 [http://dx.doi.org/10.1038/s41598-020-63634-z] [PMID: 32296104]

[72]
Gao, Y.; Hao, Y.; Jia, Y. Clinical efficacy analysis of dendritic cell-cytokine induced killer cell immunotherapy combined with paclitaxel-cisplatin chemotherapy in patients with advanced ovarian cancer. J. B.U.ON.: off. j. Balkan Union Oncol.,  2021, 26(2), 553-560.

[73]
van Amerongen, R.A.; Hagedoorn, R.S.; Remst, D.F.G.; Assendelft, D.C.; van der Steen, D.M.; Wouters, A.K.; van de Meent, M.; Kester, M.G.D.; de Ru, A.H.; Griffioen, M.; van Veelen, P.A.; Falkenburg, J.H.F.; Heemskerk, M.H.M. WT1-specific TCRs directed against newly identified peptides install antitumor reactivity against acute myeloid leukemia and ovarian carcinoma. J. Immunother. Cancer,  2022, 10(6), e004409.
 [http://dx.doi.org/10.1136/jitc-2021-004409] [PMID: 35728869]

[74]
Yossef, R.; Tran, E.; Deniger, D.C.; Gros, A.; Pasetto, A.; Parkhurst, M.R.; Gartner, J.J.; Prickett, T.D.; Cafri, G.; Robbins, P.F.; Rosenberg, S.A. Enhanced detection of neoantigen-reactive T cells targeting unique and shared oncogenes for personalized cancer immunotherapy. J.C.I Insight,  2018, 3(19), e122467.
 [http://dx.doi.org/10.1172/jci.insight.122467] [PMID: 30282837]

[75]
Wu, J.W.Y.; Dand, S.; Doig, L.; Papenfuss, A.T.; Scott, C.L.; Ho, G.; Ooi, J.D. T-Cell receptor therapy in the treatment of ovarian cancer: A mini review. Front. Immunol.,  2021, 12, 672502.
 [http://dx.doi.org/10.3389/fimmu.2021.672502] [PMID: 33927729]

[76]
Fan, C.A.; Reader, J.; Roque, D.M. Review of immune therapies targeting ovarian cancer. Curr. Treat. Options Oncol.,  2018, 19(12), 74.
 [http://dx.doi.org/10.1007/s11864-018-0584-3] [PMID: 30430276]

[77]
Tomar, S.; Zhang, J.; Khanal, M.; Hong, J.; Venugopalan, A.; Jiang, Q.; Sengupta, M.; Miettinen, M.; Li, N.; Pastan, I.; Ho, M.; Hassan, R. Development of highly effective anti-mesothelin hYP218 Chimeric Antigen Receptor T cells with increased tumor infiltration and persistence for treating solid tumors. Mol. Cancer Ther.,  2022, 21(7), 1195-1206.
 [http://dx.doi.org/10.1158/1535-7163.MCT-22-0073] [PMID: 35499461]

[78]
Rodriguez-Garcia, A.; Lynn, R.C.; Poussin, M.; Eiva, M.A.; Shaw, L.C.; O’Connor, R.S.; Minutolo, N.G.; Casado-Medrano, V.; Lopez, G.; Matsuyama, T.; Powell, D.J., Jr CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy. Nat. Commun.,  2021, 12(1), 877.
 [http://dx.doi.org/10.1038/s41467-021-20893-2] [PMID: 33563975]

[79]
Hyrenius-Wittsten, A.; Su, Y.; Park, M.; Garcia, J.M.; Alavi, J.; Perry, N.; Montgomery, G.; Liu, B.; Roybal, K.T. SynNotch CAR circuits enhance solid tumor recognition and promote persistent antitumor activity in mouse models. Sci. Transl. Med.,  2021, 13(591), eabd8836.
 [http://dx.doi.org/10.1126/scitranslmed.abd8836] [PMID: 33910981]

[80]
Du, H.; Hirabayashi, K.; Ahn, S.; Kren, N.P.; Montgomery, S.A.; Wang, X.; Tiruthani, K.; Mirlekar, B.; Michaud, D.; Greene, K.; Herrera, S.G.; Xu, Y.; Sun, C.; Chen, Y.; Ma, X.; Ferrone, C.R.; Pylayeva-Gupta, Y.; Yeh, J.J.; Liu, R.; Savoldo, B.; Ferrone, S.; Dotti, G. Antitumor responses in the absence of toxicity in solid tumors by targeting B7-H3 via chimeric antigen receptor T cells. Cancer Cell,  2019, 35(2), 221-237.e8.
 [http://dx.doi.org/10.1016/j.ccell.2019.01.002] [PMID: 30753824]

[81]
Chodon, T.; Lugade, A.A.; Battaglia, S.; Odunsi, K. Emerging role and future directions of immunotherapy in advanced ovarian cancer. Hematol. Oncol. Clin. North Am.,  2018, 32(6), 1025-1039.
 [http://dx.doi.org/10.1016/j.hoc.2018.07.011] [PMID: 30390758]

[82]
Galluzzi, L.; Buqué, A.; Kepp, O.; Zitvogel, L.; Kroemer, G. Immunogenic cell death in cancer and infectious disease. Nat. Rev. Immunol.,  2017, 17(2), 97-111.
 [http://dx.doi.org/10.1038/nri.2016.107] [PMID: 27748397]

[83]
Russell, S.J.; Peng, K.W. Oncolytic virotherapy: A contest between apples and oranges. Mol. Ther.,  2017, 25(5), 1107-1116.
 [http://dx.doi.org/10.1016/j.ymthe.2017.03.026] [PMID: 28392162]

[84]
Tian, L.; Xu, B.; Teng, K.Y.; Song, M.; Zhu, Z.; Chen, Y.; Wang, J.; Zhang, J.; Feng, M.; Kaur, B.; Rodriguez, L.; Caligiuri, M.A.; Yu, J. Targeting Fc receptor-mediated effects and the “don’t eat me” signal with an oncolytic virus expressing an anti-CD47 antibody to treat metastatic ovarian cancer. Clin. Cancer Res.,  2022, 28(1), 201-214.
 [http://dx.doi.org/10.1158/1078-0432.CCR-21-1248] [PMID: 34645647]

[85]
McGray, A.J.R.; Huang, R.Y.; Battaglia, S.; Eppolito, C.; Miliotto, A.; Stephenson, K.B.; Lugade, A.A.; Webster, G.; Lichty, B.D.; Seshadri, M.; Kozbor, D.; Odunsi, K. Oncolytic Maraba virus armed with tumor antigen boosts vaccine priming and reveals diverse therapeutic response patterns when combined with checkpoint blockade in ovarian cancer. J. Immunother. Cancer,  2019, 7(1), 189.
 [http://dx.doi.org/10.1186/s40425-019-0641-x] [PMID: 31315674]

[86]
Mistarz, A.; Graczyk, M.; Winkler, M.; Singh, P.K.; Cortes, E.; Miliotto, A.; Liu, S.; Long, M.; Yan, L.; Stablewski, A.; O’Loughlin, K.; Minderman, H.; Odunsi, K.; Rokita, H.; McGray, A.J.R.; Zsiros, E.; Kozbor, D. Induction of cell death in ovarian cancer cells by doxorubicin and oncolytic vaccinia virus is associated with CREB3L1 activation. Mol. Ther. Oncolytics,  2021, 23, 38-50.
 [http://dx.doi.org/10.1016/j.omto.2021.04.014] [PMID: 34632049]

[87]
Thomas, E.D.; Meza-Perez, S.; Bevis, K.S.; Randall, T.D.; Gillespie, G.Y.; Langford, C.; Alvarez, R.D. IL-12 expressing oncolytic herpes simplex virus promotes anti-tumor activity and immunologic control of metastatic ovarian cancer in mice. J. Ovarian Res.,  2016, 9(1), 70.
 [http://dx.doi.org/10.1186/s13048-016-0282-3] [PMID: 27784340]

[88]
Das, K.; Belnoue, E.; Rossi, M.; Hofer, T.; Danklmaier, S.; Nolden, T.; Schreiber, L.M.; Angerer, K.; Kimpel, J.; Hoegler, S.; Spiesschaert, B.; Kenner, L.; von Laer, D.; Elbers, K.; Derouazi, M.; Wollmann, G. A modular self-adjuvanting cancer vaccine combined with an oncolytic vaccine induces potent antitumor immunity. Nat. Commun.,  2021, 12(1), 5195.
 [http://dx.doi.org/10.1038/s41467-021-25506-6] [PMID: 34465781]

[89]
Morand, S.; Devanaboyina, M.; Staats, H.; Stanbery, L.; Nemunaitis, J. Ovarian cancer immunotherapy and personalized medicine. Int. J. Mol. Sci.,  2021, 22(12), 6532.
 [http://dx.doi.org/10.3390/ijms22126532] [PMID: 34207103]

[90]
Kandalaft, L.E.; Odunsi, K.; Coukos, G. Immune therapy opportunities in ovarian cancer. Am. Soc. Clin. Oncol. Educ. Book,  2020, 40(40), e228-e240.
 [http://dx.doi.org/10.1200/EDBK_280539] [PMID: 32412818]

[91]
Disis, M.L.; Patel, M.R.; Pant, S.; Infante, J.R.; Lockhart, A.C.; Kelly, K.; Beck, J.T.; Gordon, M.S.; Weiss, G.J.; Ejadi, S.; Taylor, M.H.; von Heydebreck, A.; Chin, K.M.; Cuillerot, J.M.; Gulley, J.L. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with previously treated, recurrent or refractory ovarian cancer: A phase Ib, open-label expansion trial. J. Clin. Oncol.,  2015, 33(Suppl. 15), 5509-5509.
 [http://dx.doi.org/10.1200/jco.2015.33.15_suppl.5509]

[92]
Wang, W.; Liu, J.R.; Zou, W. Immunotherapy in ovarian cancer. Surg. Oncol. Clin. N. Am.,  2019, 28(3), 447-464.
 [http://dx.doi.org/10.1016/j.soc.2019.02.002] [PMID: 31079799]

[93]
Corradetti, B.; Pisano, S.; Conlan, R.S.; Ferrari, M. Nanotechnology and immunotherapy in ovarian cancer: Tracing new landscapes. J. Pharmacol. Exp. Ther.,  2019, 370(3), 636-646.
 [http://dx.doi.org/10.1124/jpet.118.254979] [PMID: 30737357]

[94]
Hartnett, E.G.; Knight, J.; Radolec, M.; Buckanovich, R.J.; Edwards, R.P.; Vlad, A.M. Immunotherapy advances for epithelial ovarian cancer. Cancers,  2020, 12(12), 3733.
 [http://dx.doi.org/10.3390/cancers12123733] [PMID: 33322601]

[95]
Chu, C.S.; Kim, S.H.; June, C.H.; Coukos, G. Immunotherapy opportunities in ovarian cancer. Expert Rev. Anticancer Ther.,  2008, 8(2), 243-257.
 [http://dx.doi.org/10.1586/14737140.8.2.243] [PMID: 18279065]

[96]
Palaia, I.; Tomao, F.; Sassu, C.M.; Musacchio, L.; Benedetti Panici, P. Immunotherapy for ovarian cancer: Recent advances and combination therapeutic approaches. OncoTargets Ther.,  2020, 13, 6109-6129.
 [http://dx.doi.org/10.2147/OTT.S205950] [PMID: 32617007]

[97]
Rossi, L.; Verrico, M.; Zaccarelli, E.; Papa, A.; Colonna, M.; Strudel, M.; Vici, P.; Bianco, V.; Tomao, F. Bevacizumab in ovarian cancer: A critical review of phase III studies. Oncotarget,  2017, 8(7), 12389-12405.
 [http://dx.doi.org/10.18632/oncotarget.13310] [PMID: 27852039]

[98]
Tada, Y.; Togashi, Y.; Kotani, D.; Kuwata, T.; Sato, E.; Kawazoe, A.; Doi, T.; Wada, H.; Nishikawa, H.; Shitara, K. Targeting VEGFR2 with Ramucirumab strongly impacts effector/activated regulatory T cells and CD8+ T cells in the tumor microenvironment. J. Immunother. Cancer,  2018, 6(1), 106.
 [http://dx.doi.org/10.1186/s40425-018-0403-1] [PMID: 30314524]

[99]
Herrera, F.G.; Bourhis, J.; Coukos, G. Radiotherapy combination opportunities leveraging immunity for the next oncology practice. CA Cancer J. Clin.,  2017, 67(1), 65-85.
 [http://dx.doi.org/10.3322/caac.21358] [PMID: 27570942]

[100]
Bezu, L.; Gomes-de-Silva, L.C.; Dewitte, H.; Breckpot, K.; Fucikova, J.; Spisek, R.; Galluzzi, L.; Kepp, O.; Kroemer, G. Combinatorial strategies for the induction of immunogenic cell death. Front. Immunol.,  2015, 6, 187.
 [http://dx.doi.org/10.3389/fimmu.2015.00187] [PMID: 25964783]

[101]
Kandalaft, L.E.; Odunsi, K.; Coukos, G. Immunotherapy in ovarian cancer: Are we there yet? J. Clin. Oncol.,  2019, 37(27), 2460-2471.
 [http://dx.doi.org/10.1200/JCO.19.00508] [PMID: 31403857]

[102]
Lampert, E.J.; Zimmer, A.; Padget, M.; Cimino-Mathews, A.; Nair, J.R.; Liu, Y.; Swisher, E.M.; Hodge, J.W.; Nixon, A.B.; Nichols, E.; Bagheri, M.H.; Levy, E.; Radke, M.R.; Lipkowitz, S.; Annunziata, C.M.; Taube, J.M.; Steinberg, S.M.; Lee, J.M. Combination of PARP inhibitor Olaparib, and PD-L1 inhibitor durvalumab, in recurrent ovarian cancer: A proof-of-concept phase II study. Clin. Cancer Res.,  2020, 26(16), 4268-4279.
 [http://dx.doi.org/10.1158/1078-0432.CCR-20-0056] [PMID: 32398324]

[103]
Jiao, S.; Xia, W.; Yamaguchi, H.; Wei, Y.; Chen, M.K.; Hsu, J.M.; Hsu, J.L.; Yu, W.H.; Du, Y.; Lee, H.H.; Li, C.W.; Chou, C.K.; Lim, S.O.; Chang, S.S.; Litton, J.; Arun, B.; Hortobagyi, G.N.; Hung, M.C. PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clin. Cancer Res.,  2017, 23(14), 3711-3720.
 [http://dx.doi.org/10.1158/1078-0432.CCR-16-3215] [PMID: 28167507]

[104]
García-Martínez, E.; Pérez-Fidalgo, J.A. Immunotherapies in ovarian cancer. Eur. J. Cancer, Suppl.,  2020, 15, 87-95.
 [http://dx.doi.org/10.1016/j.ejcsup.2020.02.002] [PMID: 33240447]

[105]
Maiorano, B.A.; Maiorano, M.F.P.; Lorusso, D.; Maiello, E. Ovarian cancer in the era of immune checkpoint inhibitors: State of the art and future perspectives. Cancers,  2021, 13(17), 4438.
 [http://dx.doi.org/10.3390/cancers13174438] [PMID: 34503248]

[106]
Sharma, P.; Hu-Lieskovan, S.; Wargo, J.A.; Ribas, A. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell,  2017, 168(4), 707-723.
 [http://dx.doi.org/10.1016/j.cell.2017.01.017] [PMID: 28187290]

[107]
Chang, C.H.; Pearce, E.L. Emerging concepts of T cell metabolism as a target of immunotherapy. Nat. Immunol.,  2016, 17(4), 364-368.
 [http://dx.doi.org/10.1038/ni.3415] [PMID: 27002844]

[108]
Jin, L.; Tao, H.; Karachi, A.; Long, Y.; Hou, A.Y.; Na, M.; Dyson, K.A.; Grippin, A.J.; Deleyrolle, L.P.; Zhang, W.; Rajon, D.A.; Wang, Q.J.; Yang, J.C.; Kresak, J.L.; Sayour, E.J.; Rahman, M.; Bova, F.J.; Lin, Z.; Mitchell, D.A.; Huang, J. CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors. Nat. Commun.,  2019, 10(1), 4016.
 [http://dx.doi.org/10.1038/s41467-019-11869-4] [PMID: 31488817]

[109]
Morotti, M.; Albukhari, A.; Alsaadi, A.; Artibani, M.; Brenton, J.D.; Curbishley, S.M.; Dong, T.; Dustin, M.L.; Hu, Z.; McGranahan, N.; Miller, M.L.; Santana-Gonzalez, L.; Seymour, L.W.; Shi, T.; Van Loo, P.; Yau, C.; White, H.; Wietek, N.; Church, D.N.; Wedge, D.C.; Ahmed, A.A. Promises and challenges of adoptive T-cell therapies for solid tumours. Br. J. Cancer,  2021, 124(11), 1759-1776.
 [http://dx.doi.org/10.1038/s41416-021-01353-6] [PMID: 33782566]

[110]
Coscia, F.; Lengyel, E.; Duraiswamy, J.; Ashcroft, B.; Bassani-Sternberg, M.; Wierer, M.; Johnson, A.; Wroblewski, K.; Montag, A.; Yamada, S.D.; López-Méndez, B.; Nilsson, J.; Mund, A.; Mann, M.; Curtis, M. Multi-level proteomics identifies CT45 as a chemosensitivity mediator and immunotherapy target in ovarian cancer. Cell,  2018, 175(1), 159-170.e16.
 [http://dx.doi.org/10.1016/j.cell.2018.08.065] [PMID: 30241606]

[111]
Adashek, J.J.; Subbiah, I.M.; Matos, I.; Garralda, E.; Menta, A.K.; Ganeshan, D.M.; Subbiah, V. Hyperprogression and immunotherapy: Fact, fiction, or alternative fact? Trends Cancer,  2020, 6(3), 181-191.
 [http://dx.doi.org/10.1016/j.trecan.2020.01.005] [PMID: 32101722]

[112]
Ojalvo, L.S.; Nichols, P.E.; Jelovac, D.; Emens, L.A. Emerging immunotherapies in ovarian cancer. Discov. Med.,  2015, 20(109), 97-109.
 [PMID: 26463091]

[113]
Demircan, N.C.; Boussios, S.; Tasci, T.; Öztürk, M.A. Current and future immunotherapy approaches in ovarian cancer. Ann. Transl. Med.,  2020, 8(24), 1714-1714.
 [http://dx.doi.org/10.21037/atm-20-4499] [PMID: 33490226]

[114]
Hardwick, N.; Frankel, P.H.; Cristea, M. New approaches for immune directed treatment for ovarian cancer. Curr. Treat. Options Oncol.,  2016, 17(3), 14.
 [http://dx.doi.org/10.1007/s11864-016-0389-1] [PMID: 26942589]

[115]
Odunsi, K.; Matsuzaki, J.; James, S.R.; Mhawech-Fauceglia, P.; Tsuji, T.; Miller, A.; Zhang, W.; Akers, S.N.; Griffiths, E.A.; Miliotto, A.; Beck, A.; Batt, C.A.; Ritter, G.; Lele, S.; Gnjatic, S.; Karpf, A.R. Epigenetic potentiation of NY-ESO-1 vaccine therapy in human ovarian cancer. Cancer Immunol. Res.,  2014, 2(1), 37-49.
 [http://dx.doi.org/10.1158/2326-6066.CIR-13-0126] [PMID: 24535937]

[116]
Hanlon, D.J.; Aldo, P.B.; Devine, L.; Alvero, A.B.; Engberg, A.K.; Edelson, R.; Mor, G. Enhanced stimulation of anti-ovarian cancer CD8(+) T cells by dendritic cells loaded with nanoparticle encapsulated tumor antigen. Am. J. Reprod. Immunol.,  2011, 65(6), 597-609.
 [http://dx.doi.org/10.1111/j.1600-0897.2010.00968.x] [PMID: 21241402]

[117]
Rodriguez-Garcia, A.; Minutolo, N.G.; Robinson, J.M.; Powell, D.J. T-cell target antigens across major gynecologic cancers. Gynecol. Oncol.,  2017, 145(3), 426-435.
 [http://dx.doi.org/10.1016/j.ygyno.2017.03.510] [PMID: 28377094]

[118]
Greaves, M. Evolutionary determinants of cancer. Cancer Discov.,  2015, 5(8), 806-820.
 [http://dx.doi.org/10.1158/2159-8290.CD-15-0439] [PMID: 26193902]

[119]
Odunsi, K. Immunotherapy in ovarian cancer. Ann. Oncol.,  2017, 28(Suppl. 8), 1-7.
 [http://dx.doi.org/10.1093/annonc/mdx444]

[120]
McGranahan, N.; Swanton, C. Cancer evolution constrained by the immune microenvironment. Cell,  2017, 170(5), 825-827.
 [http://dx.doi.org/10.1016/j.cell.2017.08.012] [PMID: 28841415]

[121]
Ghisoni, E.; Imbimbo, M.; Zimmermann, S.; Valabrega, G. Ovarian cancer immunotherapy: Turning up the heat. Int. J. Mol. Sci.,  2019, 20(12), 2927.
 [http://dx.doi.org/10.3390/ijms20122927] [PMID: 31208030]

[122]
McCloskey, C.; Rodriguez, G.; Galpin, K.; Vanderhyden, B. Ovarian cancer immunotherapy: Preclinical models and emerging therapeutics. Cancers,  2018, 10(8), 244.
 [http://dx.doi.org/10.3390/cancers10080244] [PMID: 30049987]
Cite As
Current Women`s Health Reviews

Recent Developments in Combinatorial Immunotherapy towards Ovarian Cancer

Abstract

Graphical Abstract
