Tumor infiltrating CD8/CD103/TIM-3-expressing lymphocytes in epithelial ovarian cancer co-express CXCL13 and associate with improved survival

Abstract

Reactivation of tumor infiltrating T lymphocytes (TILs) with immune checkpoint inhibitors or co-stimulators has proven to be an effective anti-cancer strategy for a broad range of malignancies. However, epithelial ovarian cancer (EOC) remains largely refractory to current T cell-targeting immunotherapeutics. Therefore, identification of novel immune checkpoint targets and biomarkers with prognostic value for EOC is warranted. Combining multicolor immunofluorescent staining’s with single cell RNA-sequencing analysis, we here identified a TIM-3/CXCL13-positive tissue-resident memory (CD8/CD103-positive) T cell (Trm) population in EOC. Analysis of a cohort of ~175 patients with high-grade serous EOC revealed TIM-3-positive Trm were significantly associated with improved patient survival. As CXCL13-positive CD8-positive T cells have been strongly linked to patient response to anti-PD1 immune checkpoint blockade, combinatorial TIM-3 and PD-1 blockade therapy may be of interest for the (re)activation of anti-cancer immunity in EOC.

Recent advances in understanding the immune microenvironment in ovarian cancer

“…Furthermore, the inhibition of TNFRSF1B led to a notable modification of the immune microenvironment in an OC mouse model, resulting in suppressed tumor growth. These findings highlight the potential clinical significance of targeting TNFRSF1B for immunotherapy and enhance our understanding of the factors contributing to the limited success observed in OC immunotherapeutic approaches (145). Yakubovich et al reported that cancer cells that migrated into/out of tumors possessed more mesenchymal stromal cells than those that exited and deserted tumors.…”