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

• Published in: Frontiers in immunology 2022-10, Vol.13, p.1031746-1031746
• Main Authors: Vlaming, Martijn, Bilemjian, Vrouyr, Freile, Jimena Álvarez, Melo, Vinicio, Plat, Annechien, Huls, Gerwin, Nijman, Hans W., de Bruyn, Marco, Bremer, Edwin
• Format: Article
• Language: English
• Subjects: CXCL13; epithelial ovarian cancer; Immunology; RNA-seq; TIM-3; tumor infiltrating lymphocytes
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.1031746

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.