{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:22:59Z","timestamp":1787822579022,"version":"build-2784847793"},"reference-count":76,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Epithelial ovarian cancer (EOC) comprises biologically and immunologically distinct histotypes and frequently develops within a chronically inflamed tumor microenvironment, particularly in advanced disease with malignant ascites. This narrative review revisits translational observations from the 1990s\u20132000s showing impaired lymphomonocyte proliferation, altered Fas\/CD25 signaling, and abundant cytokine release in ovarian cancer effusions. These findings are interpreted as direct evidence of dysfunctional immune activation, but not as retrospective proof of T-cell exhaustion according to contemporary molecular, transcriptional, epigenetic, or functional definitions. Modern single-cell and spatial studies provide independent evidence that malignant ascites is a dynamic ecosystem containing heterogeneous T-cell and macrophage states and that immune architecture differs across anatomical compartments and histotypes. Within this framework, cytokine signaling, macrophage plasticity, iron\/redox biology, ferroptosis susceptibility, adipocyte\u2013tumor crosstalk, and systemic metabolic dysfunction are considered at different levels of evidentiary strength, with ovarian cancer-specific data distinguished from pan-cancer or preclinical extrapolation. Clinical experience with immune-checkpoint inhibitors further illustrates the distinction between immune-cell presence and effective immunity: single-agent activity has generally been modest, whereas the phase III ENGOT-ov65\/KEYNOTE-B96 trial demonstrates that clinically meaningful benefit can emerge in an appropriate therapeutic and biomarker-selected context. We propose that \u201cinflammation without effective immunity\u201d is best viewed as an overarching, histotype- and context-dependent immunometabolic framework rather than a uniform ovarian cancer phenotype. The concept remains hypothesis-generating and requires prospective validation before biomarker or therapeutic implementation.<\/jats:p>","DOI":"10.3390\/cancers18172782","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:00:35Z","timestamp":1787821235000},"page":"2782","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammation Without Effective Immunity in Ovarian Cancer: From Early Translational Observations to Histotype-Dependent Immunometabolic Ecosystems"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4731-8230","authenticated-orcid":false,"given":"Manuela","family":"Neri","sequence":"first","affiliation":[{"name":"Department of Gynecological Oncology, Azienda di Rilievo Nazionale ed Alta Specializzazione \u201cG. Brotzu\u201d, 09121 Cagliari, Italy"},{"name":"Department of Oncological Surgery, Azienda di Rilievo Nazionale ed Alta Specializzazione \u201cG. Brotzu\u201d, 09121 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1788-5322","authenticated-orcid":false,"given":"Paolo Albino","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Department of Oncological Surgery, Azienda di Rilievo Nazionale ed Alta Specializzazione \u201cG. Brotzu\u201d, 09121 Cagliari, Italy"},{"name":"Department of Thoracic Surgery, Azienda di Rilievo Nazionale ed Alta Specializzazione \u201cG. Brotzu\u201d, 09121 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Vallerino","sequence":"additional","affiliation":[{"name":"Department of Gynecological Oncology, Azienda di Rilievo Nazionale ed Alta Specializzazione \u201cG. Brotzu\u201d, 09121 Cagliari, Italy"},{"name":"Department of Oncological Surgery, Azienda di Rilievo Nazionale ed Alta Specializzazione \u201cG. Brotzu\u201d, 09121 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5387-4068","authenticated-orcid":false,"given":"Gabriele","family":"Sole","sequence":"additional","affiliation":[{"name":"Department of Oncological Surgery, Azienda di Rilievo Nazionale ed Alta Specializzazione \u201cG. Brotzu\u201d, 09121 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Macci\u00f2","sequence":"additional","affiliation":[{"name":"Department of Gynecological Oncology, Azienda di Rilievo Nazionale ed Alta Specializzazione \u201cG. Brotzu\u201d, 09121 Cagliari, Italy"},{"name":"Department of Oncological Surgery, Azienda di Rilievo Nazionale ed Alta Specializzazione \u201cG. Brotzu\u201d, 09121 Cagliari, Italy"},{"name":"Department of Surgical Sciences, University of Cagliari, SS 554 km 4.500, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16061","DOI":"10.1038\/nrdp.2016.61","article-title":"Ovarian cancer","volume":"2","author":"Matulonis","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/S0140-6736(18)32552-2","article-title":"Epithelial ovarian cancer","volume":"393","author":"Lheureux","year":"2019","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1200\/JCO.19.00508","article-title":"Immunotherapy in Ovarian Cancer: Are We There Yet?","volume":"37","author":"Kandalaft","year":"2019","journal-title":"J. Clin. 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