Heterogeneity of immune microenvironment in ovarian cancer and its clinical significance: a retrospective study

Abstract

Treatment of ovarian cancer (OC) remains the biggest challenge among gynecological malignancies. Immune checkpoint blockade therapy is promising in many cancers but shows low response rates in OC because of its heterogeneity. Although the biological and molecular heterogeneity of OC has been extensively investigated, heterogeneity of immune microenvironment remains elusive. We have collected the expression profiles of 3071 OC patients from 22 publicly available datasets. CIBERSORT was applied to infer the infiltration fraction of 22 immune cells among 2086 patients with CIBERSORT P < .05. We then explored the heterogeneity landscape of immune microenvironment in OC at three levels (immune infiltration, prognostic relevance of immune infiltration, immune checkpoint expression patterns). Multivariable Cox regression model was used to investigate the associations between survival risk and immune infiltration. Constructed immune risk score stratified patients with significantly different survival risk (HR: 1.47, 95% CI: 1.31–1.66, P < .0001). The immune infiltration landscape, prognostic relevance of immune cells, and expression patterns of 79 immune checkpoints exhibited remarkable clinicopathological heterogeneity. For instance, M1 macrophages were significantly associated with better outcomes among patients with high-grade, late-stage, type-II OC (HR: 0.77–0.83), and worse outcomes among patients with type-I OC (HR: 1.78); M2 macrophages were significantly associated with worse outcomes among patients with high-grade, type-II OC (HR: 1.14–1.17); Neutrophils were significantly associated with worse outcomes among patients with high-grade, late-stage, type-I OC (HR: 1.14–1.73). The heterogeneous landscape of immune microenvironment presented in this study provided new insights into prognostic prediction and tailored immunotherapy of OC.