Inflammation Without Effective Immunity in Ovarian Cancer: From Early Translational Observations to Histotype-Dependent Immunometabolic Ecosystems

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–2000s 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–tumor 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 “inflammation without effective immunity” 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.