Tumor Immune Microenvironment and Checkpoint Inhibition in Clear Cell Ovarian Carcinoma: Bridging Tumor Biology and Clinical Application in Immunotherapy

Clear cell ovarian carcinoma is a rare and aggressive histologic subtype of epithelial ovarian cancer, characterized by a chemoresistant phenotype and distinct immunogenomic features. Despite early-phase trials showing a limited response to immune checkpoint inhibitors (ICIs), emerging evidence reveals a biologically diverse tumor immune microenvironment, with implications for the efficacy of immunotherapies. Preclinical studies highlight paradoxical associations between immune infiltration and prognosis, as well as genomic drivers—including KRAS, MYC, PI3KCA, TP53, PTEN, and ARID1A—that shape immune evasion and checkpoint ligand expression. Clinically, ICI monotherapy yields modest benefit, while combination regimens—particularly dual checkpoint blockade and targeted co-inhibition—offer improved outcomes. Biomarkers such as PD-L1 CPS ≥ 1%, ARID1A mutations, elevated tumor mutational burden, and PIK3CA alterations emerge as promising predictors of therapeutic response. This review integrates current preclinical and clinical data to propose a precision immunotherapy framework tailored to the immunogenomic landscape of clear cell ovarian carcinoma.