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Despite advances in surgery, chemotherapy, radiotherapy, targeted therapies, and immunotherapy, these cancers remain major causes of cancer-related morbidity and mortality worldwide. Signal Transducer and Activator of Transcription 3 (STAT3) is frequently activated in these tumor types, where its biological and clinical relevance varies according to disease context, histological subtype, and molecular characteristics. In addition to tumor-intrinsic functions regulating proliferation, survival, angiogenesis, and stemness, STAT3 participates in dynamic interactions between malignant cells and the tumor microenvironment (TME), integrating inflammatory, metabolic, and stromal signals. Persistent STAT3 activation has been associated with immunosuppressive changes involving macrophage polarization, myeloid-derived suppressor cell expansion, dendritic cell dysfunction, regulatory T-cell accumulation, and impaired cytotoxic lymphocyte activity, although the extent and mechanisms of these effects differ among tumor types and experimental contexts. Metabolic alterations, including enhanced glycolysis, lactate accumulation, and hypoxia, may further interact with STAT3-dependent signaling and influence communication between tumor and stromal or immune compartments. In this review, we examine STAT3 as a signaling node linking tumor metabolism with immune regulation in cervical, ovarian, and endometrial cancers, while emphasizing disease- and subtype-specific differences. We summarize current evidence on STAT3-mediated tumor\u2013microenvironment communication and discuss emerging STAT3-targeted therapeutic strategies. Finally, we highlight challenges related to biological heterogeneity, the lack of validated predictive biomarkers, and patient stratification that currently limit the clinical translation of STAT3-directed approaches.<\/jats:p>","DOI":"10.3390\/cancers18182960","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:34:01Z","timestamp":1789378441000},"page":"2960","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond Tumor-Intrinsic STAT3: Integrating Metabolic and Immune Communication in the Tumor Microenvironment of Cervical, Ovarian, and Endometrial Cancers"],"prefix":"10.3390","volume":"18","author":[{"given":"Larissa Fonseca","family":"Marques","sequence":"first","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo (ICB-USP), S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiane Cristina","family":"Colunna","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo (ICB-USP), S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7890-0987","authenticated-orcid":false,"given":"Jordy Alexander Lasso","family":"Larco","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo (ICB-USP), S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4434-0787","authenticated-orcid":false,"given":"Francisco C\u00e2ndido do Nascimento","family":"Pombo","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo (ICB-USP), S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4707-2912","authenticated-orcid":false,"given":"Ana Paula","family":"Lepique","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences, University of S\u00e3o Paulo (ICB-USP), S\u00e3o Paulo 05508-000, Brazil"},{"name":"Comprehensive Center for Precision Oncology, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"},{"name":"National Institute of Science and Technology for Research in Infectious and Chronic Diseases of the Mucosa and Skin (INCT Mucosa and Skin), Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"04155","DOI":"10.7189\/jogh.14.04155","article-title":"Global Burden of Gynaecological Cancers in 2022 and Projections to 2050","volume":"14","author":"Zhu","year":"2024","journal-title":"J. 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