Abstract
<title>Abstract</title> <p> <bold>Background</bold> The greater omentum represents a predominant metastatic site in advanced ovarian cancer. MUC16 drives tumor progression and treatment resistance by shaping an immunosuppressive tumor microenvironment. Nevertheless, the association between MUC16 and the immune microenvironment within ovarian cancer omental metastatic lesions remains undefined. <bold>Methods</bold> A total of 40 omental metastatic tissue specimens from ovarian cancer patients were analyzed via immunohistochemistry and multiplex immunohistochemistry staining. The Timer3.0 database was utilized for external validation of our clinical cohort findings. <bold>Results</bold> Elevated MUC16 expression in omental metastatic lesions was significantly correlated with unfavorable clinical outcomes. Mature tertiary lymphoid structures (mTLS), CD3⁺ T cells and CD21⁺ dendritic cells were positively linked to improved prognosis, while CD20⁺ B cells were associated with worse survival. Further correlation analyses demonstrated that MUC16 expression was negatively associated with mTLS counts and CD3⁺ T cell density, yet no obvious differences were observed in the spatial distribution of CD3⁺ T cells between MUC16 high and low expression groups. Consistent with our specimen-based results, database analysis indicated that low MUC16 expression was correlated with prolonged overall survival (OS) and decreased infiltration of effector immune cells including CD8⁺ T cells. <bold>Conclusions</bold> High MUC16 expression in ovarian cancer omental metastatic lesions predicts poor prognosis. MUC16 may participate in reshaping the immunosuppressive immune microenvironment through its association with impaired mTLS formation and decreased CD3⁺ T cell infiltration. MUC16 could serve as a reliable prognostic biomarker and a potential candidate target for immunotherapy in ovarian cancer patients with omental metastasis. </p>