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. 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.
- Single cell mRNA sequencing data analysis. - Immunohistochemical staining, image acquisition and analysis. Tumor Infiltrated Lymphocyte flow cytometric analysis.
A cohort of EOC core samples was evaluated for the presence of tumor infiltrating CD8/CD103/TIM-3triple-positive T cells and subsequently correlated with patient survival. Interestingly, increased tumor infiltration of CD8/CD103/TIM-3triple-positive cells associated with improved patient survival in EOC, suggesting that CD8/CD103/TIM-3triple-positive TILs can serve as a prognostic marker for EOC. In line with this finding, a single-cell tumor immune transcriptomic dataset revealed upregulation of TIM-3, CXCL13 and CD103 within the terminally exhausted CD8-positive T cell fraction. Confirmatory flowcytometric evaluation of CXCL13 expression on isolated EOC TILs revealed that CXCL13 was predominantly found within the CD8/CD103/TIM-3triple-positive fraction compared to it’s single- and double-positive counterparts.
TIM-3 itself or as surrogate marker for prognostically favorable CXCL13-positive CD8-positive TILs may have prognostic value. 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.
The author.
European Union H2020 Programme.
The author has declared no conflicts of interest.