{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T09:54:12Z","timestamp":1781517252436,"version":"3.54.1"},"reference-count":162,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T00:00:00Z","timestamp":1781395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3600304"],"award-info":[{"award-number":["2022YFC3600304"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2704700"],"award-info":[{"award-number":["2022YFC2704700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Cadre Health Care Committee of Sichuan Province, China","award":["2023-1701"],"award-info":[{"award-number":["2023-1701"]}]},{"name":"Tianfu Jincheng Laboratory","award":["TFJCPI20250037"],"award-info":[{"award-number":["TFJCPI20250037"]}]},{"name":"Sichuan Cadre Health Research Project","award":["2026-1702"],"award-info":[{"award-number":["2026-1702"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Immune checkpoint inhibitors targeting the PD-1 (Programmed Cell Death Protein 1)\/PD-L1 (Programmed Death-Ligand 1) axis have transformed cancer therapeutics, yet their efficacy in gynecologic malignancies particularly high-grade serous ovarian carcinoma remains disappointingly limited. This therapeutic resistance stems from a highly orchestrated, multidimensional immunosuppressive tumor microenvironment (TME) characterized by the convergent actions of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and an inhibitory cytokine network (IL-10, TGF-\u03b2, VEGF). Emerging evidence positions TIGIT (T-cell immunoreceptor with immunoglobulin and ITIM domain) as a master checkpoint integrator that coordinately regulates CD8+ T-cell exhaustion, NK-cell dysfunction, and Treg-mediated suppression. Dual blockade of PD-1 and TIGIT represents a mechanistically rational strategy to dismantle this immunosuppressive fortress. This review synthesizes current understanding of the gynecologic TME architecture, delineates the molecular and cellular basis for TIGIT\/PD-1 synergy, critically evaluates ongoing clinical translation efforts, and proposes an integrative framework leveraging spatial transcriptomics, single-cell resolution immunoprofiling, and patient-derived experimental models to accelerate biomarker-driven therapeutic development.<\/jats:p>","DOI":"10.3390\/ijms27125373","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:57:58Z","timestamp":1781513878000},"page":"5373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond PD-1\/PD-L1: Reprogramming the Gynecologic Tumor Microenvironment by Targeting TIGIT and Myeloid Suppression"],"prefix":"10.3390","volume":"27","author":[{"given":"Shanza","family":"Waseem","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Tianfu Jincheng Laboratory, Chengdu 610041, China"},{"name":"Laboratory of Stem Cell &Embryo Development, West China Second Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0374-8076","authenticated-orcid":false,"given":"Jun","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Tianfu Jincheng Laboratory, Chengdu 610041, China"},{"name":"Laboratory of Stem Cell &Embryo Development, West China Second Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0908-3848","authenticated-orcid":false,"given":"Xue","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Tianfu Jincheng Laboratory, Chengdu 610041, China"},{"name":"Laboratory of Stem Cell &Embryo Development, West China Second Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103094","DOI":"10.1016\/j.ctrv.2026.103094","article-title":"Immunotherapy with anti-PD-1 or PD-L1 in advanced ovarian cancer: A meta-analysis of randomized trials","volume":"144","author":"Vida","year":"2026","journal-title":"Cancer Treat. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/s41571-024-00937-4","article-title":"Immunotherapy for ovarian cancer: Towards a tailored immunophenotype-based approach","volume":"21","author":"Ghisoni","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_3","unstructured":"Flynn, J.P., and Gerriets, V. (2026, April 26). Pembrolizumab, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK546616\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1200\/EDBK_280503","article-title":"A Review of Immune Checkpoint Blockade Therapy in Endometrial Cancer","volume":"40","author":"Green","year":"2020","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e38888","DOI":"10.1016\/j.heliyon.2024.e38888","article-title":"Examining the evidence for immune checkpoint therapy in high-grade serous ovarian cancer","volume":"10","author":"Connor","year":"2024","journal-title":"Heliyon"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/s41568-022-00503-z","article-title":"Immunobiology of high-grade serous ovarian cancer: Lessons for clinical translation","volume":"22","author":"Kandalaft","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","first-page":"1","article-title":"T cell exhaustion and senescence for ovarian cancer immunotherapy","volume":"104\u2013105","author":"Zhao","year":"2024","journal-title":"Semin. Cancer Biol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Worzfeld, T., Pogge von Strandmann, E., Huber, M., Adhikary, T., Wagner, U., Reinartz, S., and M\u00fcller, R. (2017). The Unique Molecular and Cellular Microenvironment of Ovarian Cancer. Front. Oncol., 7.","DOI":"10.3389\/fonc.2017.00024"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.ygyno.2018.01.014","article-title":"Tumor associated macrophages in gynecologic cancers","volume":"149","author":"Krishnan","year":"2018","journal-title":"Gynecol. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chaudhary, B., and Elkord, E. (2016). Regulatory T Cells in the Tumor Microenvironment and Cancer Progression: Role and Therapeutic Targeting. Vaccines, 4.","DOI":"10.3390\/vaccines4030028"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s11670-012-0130-y","article-title":"Overexpression and immunosuppressive functions of transforming growth factor 1, vascular endothelial growth factor and interleukin-10 in epithelial ovarian cancer","volume":"24","author":"Liu","year":"2012","journal-title":"Chin. J. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1038\/s43018-024-00870-6","article-title":"TIGIT and PD-L1 co-blockade promotes clonal expansion of multipotent, non-exhausted antitumor T cells by facilitating co-stimulation","volume":"5","author":"Nutsch","year":"2024","journal-title":"Nat. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s12943-023-01800-3","article-title":"Co-inhibition of TIGIT and PD-1\/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials","volume":"22","author":"Chu","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2","DOI":"10.5483\/BMBRep.2021.54.1.229","article-title":"Hitting the complexity of the TIGIT-CD96-CD112R-CD226 axis for next-generation cancer immunotherapy","volume":"54","author":"Jin","year":"2021","journal-title":"BMB Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"835","DOI":"10.3892\/or.2021.7943","article-title":"CD155\/TIGIT, a novel immune checkpoint in human cancers (Review)","volume":"45","author":"Liu","year":"2021","journal-title":"Oncol. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s11912-018-0740-8","article-title":"Combination Immune Checkpoint Blockade Strategies to Maximize Immune Response in Gynecological Cancers","volume":"20","author":"Liu","year":"2018","journal-title":"Curr. Oncol. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.ccell.2022.01.001","article-title":"Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments","volume":"40","author":"Kumagai","year":"2022","journal-title":"Cancer Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s00262-014-1636-6","article-title":"Activated regulatory and memory T-cells accumulate in malignant ascites from ovarian carcinoma patients","volume":"64","author":"Landskron","year":"2015","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Shao, B., Sun, B., and Xiao, Z. (2025). Transcriptome Analysis Unravels CD4+ T-Cell and Treg-Cell Differentiation in Ovarian Cancer. Biomolecules, 15.","DOI":"10.3390\/biom15091241"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8326","DOI":"10.1158\/1078-0432.CCR-05-1244","article-title":"The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer","volume":"11","author":"Wolf","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1007\/s00262-015-1753-x","article-title":"Regulatory T cells, inherited variation, and clinical outcome in epithelial ovarian cancer","volume":"64","author":"Knutson","year":"2015","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.intimp.2018.12.051","article-title":"Follicular regulatory T cells infiltrated the ovarian carcinoma and resulted in CD8 T cell dysfunction dependent on IL-10 pathway","volume":"68","author":"Li","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.jaci.2009.02.011","article-title":"IL-2- and CD25-dependent immunoregulatory mechanisms in the homeostasis of T-cell subsets","volume":"123","author":"Krieg","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7529","DOI":"10.1073\/pnas.1103782108","article-title":"CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis","volume":"108","author":"McNally","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Brzostek, J., Gascoigne, N.R., and Rybakin, V. (2016). Cell Type-Specific Regulation of Immunological Synapse Dynamics by B7 Ligand Recognition. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00024"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.immuni.2014.02.012","article-title":"Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses","volume":"40","author":"Joller","year":"2014","journal-title":"Immunity"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e2023739118","DOI":"10.1073\/pnas.2023739118","article-title":"Treg-expressed CTLA-4 depletes CD80\/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells","volume":"118","author":"Tekguc","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"145","DOI":"10.4049\/jimmunol.1402381","article-title":"Divergent Phenotypes of Human Regulatory T Cells Expressing the Receptors TIGIT and CD226","volume":"195","author":"Fuhrman","year":"2015","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"De Cicco, P., Ercolano, G., and Ianaro, A. (2020). The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01680"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1010428318776485","DOI":"10.1177\/1010428318776485","article-title":"Myeloid-derived suppressor cells and their role in gynecological malignancies","volume":"40","author":"Mabuchi","year":"2018","journal-title":"Tumour Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"76843","DOI":"10.18632\/oncotarget.20164","article-title":"Ascites-derived IL-6 and IL-10 synergistically expand CD14+HLA-DR-\/low myeloid-derived suppressor cells in ovarian cancer patients","volume":"8","author":"Wu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ok\u0142a, K., Czerwonka, A., Wawruszak, A., Bobi\u0144ski, M., Bilska, M., Tarkowski, R., Bednarek, W., Wertel, I., and Kotarski, J. (2019). Clinical Relevance and Immunosuppressive Pattern of Circulating and Infiltrating Subsets of Myeloid-Derived Suppressor Cells (MDSCs) in Epithelial Ovarian Cancer. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00691"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5839","DOI":"10.1158\/0008-5472.CAN-04-0465","article-title":"Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses","volume":"64","author":"Rodriguez","year":"2004","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1182\/blood-2006-06-031856","article-title":"L-arginine availability regulates T-lymphocyte cell-cycle progression","volume":"109","author":"Rodriguez","year":"2007","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5693","DOI":"10.4049\/jimmunol.0900092","article-title":"Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells","volume":"182","author":"Corzo","year":"2009","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1084\/jem.20101956","article-title":"Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells","volume":"208","author":"Molon","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1158\/0008-5472.CAN-09-2587","article-title":"Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine","volume":"70","author":"Srivastava","year":"2010","journal-title":"Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s00726-011-0867-5","article-title":"The oxidative stress-inducible cystine\/glutamate antiporter, system xc\u2212: Cystine supplier and beyond","volume":"42","author":"Conrad","year":"2012","journal-title":"Amino Acids"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1111\/apt.15226","article-title":"Myeloid-derived suppressor cells induce regulatory T cells in chronically HBV infected patients with high levels of hepatitis B surface antigen and persist after antiviral therapy","volume":"49","author":"Pal","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Goldmann, O., Nwofor, O.V., Chen, Q., and Medina, E. (2024). Mechanisms underlying immunosuppression by regulatory cells. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1328193"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ccr.2005.10.012","article-title":"TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance","volume":"8","author":"Thomas","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.semcancer.2012.05.004","article-title":"TGF-\u03b2-induced epithelial-mesenchymal transition: A link between cancer and inflammation","volume":"22","author":"Fuxe","year":"2012","journal-title":"Semin. Cancer Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9830","DOI":"10.1021\/acsnano.8b00967","article-title":"Local Blockade of Interleukin 10 and C-X-C Motif Chemokine Ligand 12 with Nano-Delivery Promotes Antitumor Response in Murine Cancers","volume":"12","author":"Shen","year":"2018","journal-title":"ACS Nano"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1002\/eji.200838674","article-title":"Tumor-mediated down-regulation of MHC class II in DC development is attributable to the epigenetic control of the CIITA type I promoter","volume":"39","author":"Choi","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1385\/IR:23:2-3:263","article-title":"VEGF as a mediator of tumor-associated immunodeficiency","volume":"23","author":"Ohm","year":"2001","journal-title":"Immunol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1158\/1078-0432.CCR-16-0387","article-title":"Expression of Vascular Endothelial Growth Factor in Ovarian Cancer Inhibits Tumor Immunity through the Accumulation of Myeloid-Derived Suppressor Cells","volume":"23","author":"Horikawa","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1084\/jem.20140559","article-title":"VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors","volume":"212","author":"Voron","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1002\/JLB.5RU0222-082R","article-title":"Direct and indirect regulation of the tumor immune microenvironment by VEGF","volume":"111","author":"Zhang","year":"2022","journal-title":"J. Leukoc. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/s41588-020-0630-5","article-title":"Unraveling tumor-immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy","volume":"52","author":"Cybulska","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e70538","DOI":"10.1002\/ctm2.70538","article-title":"Single-cell landscape of the tumour immune microenvironment in human gynaecologic malignancies","volume":"15","author":"Yin","year":"2025","journal-title":"Clin. Transl. Med."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Pizzimenti, C., Fiorentino, V., Pepe, L., Franchina, M., Ruggeri, C., Ercoli, A., Ciappina, G., Berretta, M., Tuccari, G., and Ieni, A. (2025). Predictive Biomarkers for Immunotherapy in Endometrial Carcinoma. Cancers, 17.","DOI":"10.3390\/cancers17152420"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00795-021-00290-w","article-title":"Prediction of treatment response from the microenvironment of tumor immunity in cervical cancer patients treated with chemoradiotherapy","volume":"54","author":"Someya","year":"2021","journal-title":"Med. Mol. Morphol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"104603","DOI":"10.1016\/j.critrevonc.2024.104603","article-title":"The multiple facets of ovarian high grade serous carcinoma: A review on morphological, immunohistochemical and molecular features","volume":"208","author":"Santoro","year":"2025","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4485","DOI":"10.2147\/OTT.S324641","article-title":"Endometrial Tumors with MSI-H and dMMR Share a Similar Tumor Immune Microenvironment","volume":"14","author":"Song","year":"2021","journal-title":"Onco Targets Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"200238","DOI":"10.1016\/j.tvr.2022.200238","article-title":"Cervical cancer therapies: Current challenges and future perspectives","volume":"13","author":"Burmeister","year":"2022","journal-title":"Tumour Virus Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s42003-023-05733-x","article-title":"Single-cell analysis reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of ovarian cancer","volume":"7","author":"Zhang","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejca.2016.02.026","article-title":"CD103 defines intraepithelial CD8+ PD1+ tumour-infiltrating lymphocytes of prognostic significance in endometrial adenocarcinoma","volume":"60","author":"Workel","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.1002\/ijc.28309","article-title":"Tumor-infiltrating CD14-positive myeloid cells and CD8-positive T-cells prolong survival in patients with cervical carcinoma","volume":"133","author":"Ramwadhdoebe","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/s41416-020-01184-x","article-title":"Infiltrating T-cell markers in cervical carcinogenesis: A systematic review and meta-analysis","volume":"124","author":"Litwin","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Sato, S., Matsushita, H., Shintani, D., Kobayashi, Y., Fujieda, N., Yabuno, A., Nishikawa, T., Fujiwara, K., Kakimi, K., and Hasegawa, K. (2022). Association between effector-type regulatory T cells and immune checkpoint expression on CD8+ T cells in malignant ascites from epithelial ovarian cancer. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-09534-z"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Suto, A., Minaguchi, T., Qi, N., Fujieda, K., Itagaki, H., Tenjimbayashi, Y., Shikama, A., Tasaka, N., Akiyama, A., and Nakao, S. (2024). CD25+FOXP3+CD45RA\u2212 regulatory T-cell infiltration as a prognostic biomarker for endometrial carcinoma. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12851-0"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.bbrc.2020.07.039","article-title":"Selective binding of mitophagy receptor protein Bcl-rambo to LC3\/GABARAP family proteins","volume":"530","author":"Li","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_63","first-page":"128","article-title":"Expressions of Immune Negative Regulator FoxP3+Treg and PD-L1 Protein in the Immune Microenvironment of Cervical Lesion","volume":"39","author":"Ma","year":"2017","journal-title":"Zhongguo Yi Xue Ke Xue Yuan Xue Bao"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Mabuchi, S., Sasano, T., and Komura, N. (2021). Targeting Myeloid-Derived Suppressor Cells in Ovarian Cancer. Cells, 10.","DOI":"10.3390\/cells10020329"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Mabuchi, S., and Sasano, T. (2021). Myeloid-Derived Suppressor Cells as Therapeutic Targets in Uterine Cervical and Endometrial Cancers. Cells, 10.","DOI":"10.3390\/cells10051073"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1172\/JCI80445","article-title":"TIGIT and PD-1 impair tumor antigen-specific CD8+ T cells in melanoma patients","volume":"125","author":"Chauvin","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1002\/hep.31466","article-title":"Transcriptome Profiling Identifies TIGIT as a Marker of T-Cell Exhaustion in Liver Cancer","volume":"73","author":"Ostroumov","year":"2021","journal-title":"Hepatology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.intimp.2017.08.017","article-title":"Prognostic value of tumor PD-L1 expression combined with CD8+ tumor infiltrating lymphocytes in high grade serous ovarian cancer","volume":"52","author":"Wang","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_69","first-page":"3185","article-title":"PD-L1 expression with QR1 and E1L3N antibodies according to histological ovarian cancer subtype: A series of 232 cases","volume":"65","author":"Ilenko","year":"2021","journal-title":"Eur. J. Histochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5652","DOI":"10.18632\/oncotarget.23790","article-title":"Microsatellite instability is a biomarker for immune checkpoint inhibitors in endometrial cancer","volume":"9","author":"Yamashita","year":"2017","journal-title":"Oncotarget"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.ygyno.2017.03.006","article-title":"Characterization of immune regulatory molecules B7-H4 and PD-L1 in low and high grade endometrial tumors","volume":"145","author":"Bregar","year":"2017","journal-title":"Gynecol. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41379-018-0148-x","article-title":"Identification of a subset of microsatellite-stable endometrial carcinoma with high PD-L1 and CD8+ lymphocytes","volume":"32","author":"Crumley","year":"2019","journal-title":"Mod. Pathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"104084","DOI":"10.1016\/j.critrevonc.2023.104084","article-title":"Prevalence and prognostic role of PD-L1 in patients with gynecological cancers: A systematic review and meta-analysis","volume":"189","author":"Fu","year":"2023","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/modpathol.2016.64","article-title":"Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix","volume":"29","author":"Heeren","year":"2016","journal-title":"Mod. Pathol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ygyno.2016.03.008","article-title":"PD-L1 expression is associated with tumor-infiltrating T cells and favorable prognosis in high-grade serous ovarian cancer","volume":"141","author":"Webb","year":"2016","journal-title":"Gynecol. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s12672-022-00466-5","article-title":"The clinicopathological characteristics, prognosis and immune microenvironment mapping in MSI-H\/MMR-D endometrial carcinomas","volume":"13","author":"Guo","year":"2022","journal-title":"Discov. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.3802\/jgo.2023.34.e18","article-title":"Lymphocyte activation gene (LAG)-3 is a potential immunotherapeutic target for microsatellite stable, programmed death-ligand 1 (PD-L1)-positive endometrioid endometrial cancer","volume":"34","author":"Hong","year":"2023","journal-title":"J. Gynecol. Oncol."},{"key":"ref_78","first-page":"23","article-title":"The evolving role of immune checkpoint inhibitors in cervical and endometrial cancer","volume":"7","author":"Colombo","year":"2024","journal-title":"Cancer Drug Resist."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s11864-017-0504-y","article-title":"Immunotherapy in Gynecologic Cancers: Are We There Yet?","volume":"18","author":"Pakish","year":"2017","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.ygyno.2018.10.008","article-title":"Characteristics and outcomes of patients with recurrent ovarian cancer undergoing early phase immune checkpoint inhibitor clinical trials","volume":"151","author":"Hinchcliff","year":"2018","journal-title":"Gynecol. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1200\/JCO.21.01874","article-title":"Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study","volume":"40","author":"Bariani","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ygyno.2024.12.020","article-title":"Pembrolizumab in microsatellite instability-high\/mismatch repair deficient (MSI-H\/dMMR) and non-MSI-H\/non-dMMR advanced endometrial cancer: Phase 2 KEYNOTE-158 study results","volume":"193","author":"Bariani","year":"2025","journal-title":"Gynecol. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4035","DOI":"10.1200\/JCO.2017.74.5471","article-title":"Safety and Efficacy of Pembrolizumab in Advanced, Programmed Death Ligand 1-Positive Cervical Cancer: Results From the Phase Ib KEYNOTE-028 Trial","volume":"35","author":"Frenel","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1200\/JCO.18.01265","article-title":"Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study","volume":"37","author":"Chung","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3969","DOI":"10.1038\/s41467-021-24112-w","article-title":"Molecular determinants of response to PD-L1 blockade across tumor types","volume":"12","author":"Banchereau","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Maiorano, B.A., Maiorano, M.F.P., Cormio, G., Maglione, A., Lorusso, D., and Maiello, E. (2022). How Immunotherapy Modified the Therapeutic Scenario of Endometrial Cancer: A Systematic Review. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.844801"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1093\/intimm\/dxab085","article-title":"DNAM-1 versus TIGIT: Competitive roles in tumor immunity and inflammatory responses","volume":"33","author":"Shibuya","year":"2021","journal-title":"Int. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/cei.13407","article-title":"TIGIT as an emerging immune checkpoint","volume":"200","author":"Guillerey","year":"2020","journal-title":"Clin. Exp. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/cdd.2012.141","article-title":"Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells","volume":"20","author":"Liu","year":"2013","journal-title":"Cell Death Differ."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e000957","DOI":"10.1136\/jitc-2020-000957","article-title":"TIGIT in cancer immunotherapy","volume":"8","author":"Chauvin","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Conner, M., Hance, K.W., Yadavilli, S., Smothers, J., and Waight, J.D. (2022). Emergence of the CD226 Axis in Cancer Immunotherapy. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.914406"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"17647","DOI":"10.1074\/jbc.M114.572420","article-title":"T-cell immunoglobulin and ITIM domain (TIGIT) receptor\/poliovirus receptor (PVR) ligand engagement suppresses interferon-\u03b3 production of natural killer cells via \u03b2-arrestin 2-mediated negative signaling","volume":"289","author":"Li","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Paolini, R., and Molfetta, R. (2023). Dysregulation of DNAM-1-Mediated NK Cell Anti-Cancer Responses in the Tumor Microenvironment. Cancers, 15.","DOI":"10.3390\/cancers15184616"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"17858","DOI":"10.1073\/pnas.0903474106","article-title":"The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity","volume":"106","author":"Stanietsky","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Sanchez-Correa, B., Valhondo, I., Hassouneh, F., Lopez-Sejas, N., Pera, A., Bergua, J.M., Arcos, M.J., Ba\u00f1as, H., Casas-Avil\u00e9s, I., and Dur\u00e1n, E. (2019). DNAM-1 and the TIGIT\/PVRIG\/TACTILE Axis: Novel Immune Checkpoints for Natural Killer Cell-Based Cancer Immunotherapy. Cancers, 11.","DOI":"10.3390\/cancers11060877"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.semcancer.2019.11.013","article-title":"Tumor intrinsic and extrinsic immune functions of CD155","volume":"65","author":"Madore","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"101405","DOI":"10.1016\/j.jhepr.2025.101405","article-title":"The dual role of TIGIT in regulatory and effector T cells in chronic liver disease","volume":"7","author":"Bozward","year":"2025","journal-title":"JHEP Rep."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Yeo, J., Ko, M., Lee, D.H., Park, Y., and Jin, H.S. (2021). TIGIT\/CD226 Axis Regulates Anti-Tumor Immunity. Pharmaceuticals, 14.","DOI":"10.3390\/ph14030200"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e004711","DOI":"10.1136\/jitc-2022-004711","article-title":"TIGIT-CD226-PVR axis: Advancing immune checkpoint blockade for cancer immunotherapy","volume":"10","author":"Chiang","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.ccell.2014.10.018","article-title":"The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function","volume":"26","author":"Bozward","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"5520","DOI":"10.1158\/1078-0432.CCR-20-0575","article-title":"IL15 Stimulation with TIGIT Blockade Reverses CD155-mediated NK-Cell Dysfunction in Melanoma","volume":"26","author":"Chauvin","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5016","DOI":"10.1038\/s41467-023-40755-3","article-title":"TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation","volume":"14","author":"Worboys","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.immuni.2022.02.005","article-title":"Mechanistic convergence of the TIGIT and PD-1 inhibitory pathways necessitates co-blockade to optimize anti-tumor CD8+ T cell responses","volume":"55","author":"Banta","year":"2022","journal-title":"Immunity"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Ge, Z., Peppelenbosch, M.P., Sprengers, D., and Kwekkeboom, J. (2021). TIGIT, the Next Step Towards Successful Combination Immune Checkpoint Therapy in Cancer. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.699895"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.it.2015.02.007","article-title":"T cell metabolic fitness in antitumor immunity","volume":"36","author":"Siska","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.4049\/jimmunol.1502464","article-title":"Suppression of Glut1 and Glucose Metabolism by Decreased Akt\/mTORC1 Signaling Drives T Cell Impairment in B Cell Leukemia","volume":"197","author":"Siska","year":"2016","journal-title":"J. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3869","DOI":"10.4049\/jimmunol.1103627","article-title":"The TIGIT\/CD226 axis regulates human T cell function","volume":"188","author":"Lozano","year":"2012","journal-title":"J. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e0027324","DOI":"10.1128\/jvi.00273-24","article-title":"Immune restoration by TIGIT blockade is insufficient to control chronic SIV infection","volume":"98","author":"Webb","year":"2024","journal-title":"J. Virol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1873607","DOI":"10.1080\/2162402X.2021.1873607","article-title":"Addition of anti-TIM3 or anti-TIGIT Antibodies to anti-PD1 Blockade Augments Human T cell Adoptive Cell Transfer","volume":"10","author":"Martinez","year":"2021","journal-title":"Oncoimmunology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1126\/science.aad0501","article-title":"Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq","volume":"352","author":"Tirosh","year":"2016","journal-title":"Science"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"5160565","DOI":"10.1155\/2019\/5160565","article-title":"Patterns of TIGIT Expression in Lymphatic Tissue, Inflammation, and Cancer","volume":"2019","author":"Blessin","year":"2019","journal-title":"Dis. Markers"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e121157","DOI":"10.1172\/jci.insight.121157","article-title":"CD226 opposes TIGIT to disrupt Tregs in melanoma","volume":"3","author":"Fourcade","year":"2018","journal-title":"JCI Insight"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1158\/2326-6066.CIR-18-0725","article-title":"Blockade of TIGIT\/CD155 Signaling Reverses T-cell Exhaustion and Enhances Antitumor Capability in Head and Neck Squamous Cell Carcinoma","volume":"7","author":"Wu","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Chen, X., Xue, L., Ding, X., Zhang, J., Jiang, L., Liu, S., Hou, H., Jiang, B., Cheng, L., and Zhu, Q. (2022). An Fc-Competent Anti-Human TIGIT Blocking Antibody Ociperlimab (BGB-A1217) Elicits Strong Immune Responses and Potent Anti-Tumor Efficacy in Pre-Clinical Models. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.828319"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/s41590-018-0132-0","article-title":"Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity","volume":"19","author":"Zhang","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1843247","DOI":"10.1080\/2162402X.2020.1843247","article-title":"TIGIT blockade enhances functionality of peritoneal NK cells with altered expression of DNAM-1\/TIGIT\/CD96 checkpoint molecules in ovarian cancer","volume":"9","author":"Maas","year":"2020","journal-title":"Oncoimmunology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1158\/1078-0432.CCR-21-2780","article-title":"A Phase 1a\/b Open-Label, Dose-Escalation Study of Etigilimab Alone or in Combination with Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumors","volume":"28","author":"Mettu","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ygyno.2025.04.579","article-title":"AdvanTIG-202: Phase 2 open-label, two-cohort multicenter study of ociperlimab plus tislelizumab and tislelizumab alone in patients with previously treated recurrent or metastatic cervical cancer","volume":"198","author":"Lee","year":"2025","journal-title":"Gynecol. Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S1470-2045(22)00226-1","article-title":"Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): Primary and follow-up analyses of a randomised, double-blind, phase 2 study","volume":"23","author":"Cho","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"4294","DOI":"10.1200\/JCO.24.00668","article-title":"Atezolizumab Combined With Platinum and Maintenance Niraparib for Recurrent Ovarian Cancer With a Platinum-Free Interval >6 Months: ENGOT-OV41\/GEICO 69-O\/ANITA Phase III Trial","volume":"42","author":"Rubio","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"101184","DOI":"10.1016\/j.esmoop.2023.101184","article-title":"Anti-TIGIT therapies for solid tumors: A systematic review","volume":"8","author":"Rousseau","year":"2023","journal-title":"ESMO Open"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.ygyno.2022.01.029","article-title":"Efficacy and safety of pembrolizumab for patients with previously treated advanced vulvar squamous cell carcinoma: Results from the phase 2 KEYNOTE-158 study","volume":"166","author":"Mileshkin","year":"2022","journal-title":"Gynecol. Oncol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e003156","DOI":"10.1136\/jitc-2021-003156","article-title":"Combination immunotherapy with nivolumab and ipilimumab in patients with rare gynecological malignancies: Results of the CA209-538 clinical trial","volume":"9","author":"Klein","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"4286","DOI":"10.1158\/1078-0432.CCR-14-2607","article-title":"Phase I Study of Pembrolizumab (MK-3475; Anti-PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors","volume":"21","author":"Patnaik","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/s41586-024-07121-9","article-title":"Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells","volume":"627","author":"Guan","year":"2024","journal-title":"Nature"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1080\/1750743X.2025.2460964","article-title":"Immune checkpoint inhibitors in gynecological cancers: A narrative review on the practice-changing trials","volume":"17","author":"Nasso","year":"2025","journal-title":"Immunotherapy"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Koshkimbayeva, G., Amirkhanova, A., Orazymbetova, A., Nurakhova, A., Maimakova, A., Duisenbayeva, A., Akhmad, N., Abilova, A., Abilbayeva, A., and Akhelova, S. (2026). Recent therapeutic advances in gynecologic oncology: Evolving roles of immunotherapy, antibody-drug conjugates, and clinical trial innovations. Front. Oncol., 15, Correction in Front. Oncol. 2026, 16, 1803643.","DOI":"10.3389\/fonc.2026.1803643"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.annonc.2021.11.002","article-title":"First-in-human phase 1 study of the anti-TIGIT antibody vibostolimab as monotherapy or with pembrolizumab for advanced solid tumors, including non-small-cell lung cancer","volume":"33","author":"Niu","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s40164-024-00543-1","article-title":"Tumor battlefield within inflamed, excluded or desert immune phenotypes: The mechanisms and strategies","volume":"13","author":"Zheng","year":"2024","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.ccell.2021.04.004","article-title":"Single-cell dissection of cellular components and interactions shaping the tumor immune phenotypes in ovarian cancer","volume":"39","author":"Hornburg","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Tiwari, A., Oravecz, T., Dillon, L.A., Italiano, A., Audoly, L., Fridman, W.H., and Clifton, G.T. (2023). Towards a consensus definition of immune exclusion in cancer. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1084887"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Benito-Lopez, J.J., Marroquin-Muci\u00f1o, M., Perez-Medina, M., Chavez-Dominguez, R., Aguilar-Cazares, D., Galicia-Velasco, M., and Lopez-Gonzalez, J.S. (2023). Partners in crime: The feedback loop between metabolic reprogramming and immune checkpoints in the tumor microenvironment. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1101503"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"El-Sayes, N., Vito, A., and Mossman, K. (2021). Tumor Heterogeneity: A Great Barrier in the Age of Cancer Immunotherapy. Cancers, 13.","DOI":"10.3390\/cancers13040806"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.semcancer.2017.04.007","article-title":"How to study and overcome tumor heterogeneity with circulating biomarkers: The breast cancer case","volume":"44","author":"Appierto","year":"2017","journal-title":"Semin. Cancer Biol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1586\/14737159.2015.1110021","article-title":"Testing for oncogenic molecular aberrations in cell-free DNA-based liquid biopsies in the clinic: Are we there yet?","volume":"15","author":"Polivka","year":"2015","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.canlet.2017.11.014","article-title":"Progress and challenges of predictive biomarkers of anti PD-1\/PD-L1 immunotherapy: A systematic review","volume":"414","author":"Teng","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1158\/1535-7163.MCT-20-0464","article-title":"Restoration of T-cell Effector Function, Depletion of Tregs, and Direct Killing of Tumor Cells: The Multiple Mechanisms of Action of a-TIGIT Antagonist Antibodies","volume":"20","author":"Preillon","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1158\/2326-6066.CIR-19-0877","article-title":"CD226hiCD8+ T Cells Are a Prerequisite for Anti-TIGIT Immunotherapy","volume":"8","author":"Jin","year":"2020","journal-title":"Cancer Immunol. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/JID.2015.404","article-title":"Melanoma Cells Control Antimelanoma CTL Responses via Interaction between TIGIT and CD155 in the Effector Phase","volume":"136","author":"Inozume","year":"2016","journal-title":"J. Investig. Dermatol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e003134","DOI":"10.1136\/jitc-2021-003134","article-title":"TIGIT\/CD155 axis mediates resistance to immunotherapy in patients with melanoma with the inflamed tumor microenvironment","volume":"9","author":"Kawashima","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1158\/1078-0432.CCR-19-3925","article-title":"Tumor CD155 Expression Is Associated with Resistance to Anti-PD1 Immunotherapy in Metastatic Melanoma","volume":"26","author":"Lepletier","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e1183","DOI":"10.1002\/cti2.1183","article-title":"Immune contexture analysis in immuno-oncology: Applications and challenges of multiplex fluorescent immunohistochemistry","volume":"9","author":"Shakya","year":"2020","journal-title":"Clin. Transl. Immunol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1186\/s13059-016-1092-z","article-title":"Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures","volume":"17","author":"Gejman","year":"2016","journal-title":"Genome Biol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1158\/2159-8290.CD-18-0044","article-title":"Mouse Models for Cancer Immunotherapy Research","volume":"8","author":"Olson","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1093\/annonc\/mdw041","article-title":"Defining the optimal murine models to investigate immune checkpoint blockers and their combination with other immunotherapies","volume":"27","author":"Sanmamed","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"McCloskey, C.W., Rodriguez, G.M., Galpin, K.J.C., and Vanderhyden, B.C. (2018). Ovarian Cancer Immunotherapy: Preclinical Models and Emerging Therapeutics. Cancers, 10.","DOI":"10.3390\/cancers10080244"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"34626","DOI":"10.1038\/s41598-025-18264-8","article-title":"ID8 cells manifest phenotypic plasticity and molecular heterogeneity of high-grade serous ovarian cancer in response to the local tissue niche","volume":"15","author":"Gupta","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.mattod.2015.05.002","article-title":"Engineering cancer microenvironments for in vitro 3-D tumor models","volume":"18","author":"Asghar","year":"2015","journal-title":"Mater. Today"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"e1400","DOI":"10.1002\/cti2.1400","article-title":"Modelling the tumor immune microenvironment for precision immunotherapy","volume":"11","author":"Mackenzie","year":"2022","journal-title":"Clin. Transl. Immunol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2093518","DOI":"10.1080\/2162402X.2022.2093518","article-title":"PD-1 blockade synergizes with oxaliplatin-based, but not cisplatin-based, chemotherapy of gastric cancer","volume":"11","author":"Liu","year":"2022","journal-title":"Oncoimmunology"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/14737140.2025.2460537","article-title":"Immune checkpoint inhibitors plus taxane-based chemotherapy for patients with advanced\/metastatic NSCLC: A systematic review and meta-analysis across different PD-L1 expression levels","volume":"25","author":"Abushanab","year":"2025","journal-title":"Expert Rev. Anticancer. Ther."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2972","DOI":"10.1016\/j.celrep.2018.11.054","article-title":"PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer","volume":"25","author":"Ding","year":"2018","journal-title":"Cell Rep."},{"key":"ref_153","first-page":"e99275","article-title":"Emerging Therapeutic Synergies: Combining PD-1 Inhibitors With Poly-ADP-Ribose Polymerase (PARP) Inhibitors in the Treatment of Gynecologic Cancers","volume":"17","author":"Loh","year":"2025","journal-title":"Cureus"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.jtho.2016.04.026","article-title":"Effect of First-Line Treatment on Myeloid-Derived Suppressor Cells\u2019 Subpopulations in the Peripheral Blood of Patients with Non-Small Cell Lung Cancer","volume":"11","author":"Koinis","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"12624","DOI":"10.1038\/ncomms12624","article-title":"Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma","volume":"7","author":"Wallin","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"He, J., Tao, J., Zhou, Y., Li, H., Feng, W., and Xu, Y. (2025). TGF-\u03b2-driven T-cell exclusion in ovarian cancer: Single-cell and spatial transcriptomic views of immune low-response states. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1698088"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"4545","DOI":"10.1038\/s41467-020-17811-3","article-title":"Selective inhibition of TGF-\u03b21 produced by GARP-expressing Tregs overcomes resistance to PD-1\/PD-L1 blockade in cancer","volume":"11","author":"Bertrand","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.intimp.2017.03.015","article-title":"Primary and acquired resistance to PD-1\/PD-L1 blockade in cancer treatment","volume":"46","author":"Wang","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"100738","DOI":"10.1016\/j.tranon.2019.12.010","article-title":"Resistance to Checkpoint Inhibition in Cancer Immunotherapy","volume":"13","author":"Barrueto","year":"2020","journal-title":"Transl. Oncol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"400","DOI":"10.4049\/jimmunol.1701041","article-title":"Metabolic Barriers to T Cell Function in Tumors","volume":"200","author":"Sugiura","year":"2018","journal-title":"J. Immunol."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Li, X., Zhong, J., Deng, X., Guo, X., Lu, Y., Lin, J., Huang, X., and Wang, C. (2021). Targeting Myeloid-Derived Suppressor Cells to Enhance the Antitumor Efficacy of Immune Checkpoint Blockade Therapy. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.754196"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Smith, A.J., Thurman, R.E., Zeng, W., Grogan, B., Lucas, S., Gutierrez, G., Heiser, R.A., Wo, S.W., Blackmarr, A., and Peterson, S. (2023). Nonfucosylation of an anti-TIGIT antibody enhances Fc\u03b3R engagement, driving innate immune activation and antitumor activity. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1280986"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5373\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T09:17:47Z","timestamp":1781515067000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,14]]},"references-count":162,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125373"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125373","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,14]]}}}