Intratumoural CD103+CD56+ ILCs are associated a with dysfunctional CD8+ T cell profile in patients with ovarian epithelial carcinoma 4835

Abstract Description Innate lymphoid cells (ILCs) with inhibitory properties have recently been identified in cancer, but the specific surface markers or transcription factors distinguishing these populations from conventional ILCs are not well-defined. In this study, we found that CD103 identifies CD56+ ILCs that are associated with poor proliferative capacity in tumor-infiltrating lymphocyte (TIL) cultures from epithelial ovarian carcinoma (EOC). These CD103+CD56+ ILCs expressed distinct surface markers (e.g., CD101, CD49a, GITR) and exhibited a unique transcriptomic profile compared to other intratumoral ILC subsets (ILC1s, ILC2s, ILC3s, NK cells). Using scRNA-seq, we discovered that tumors with a high abundance of CD103+CD56+ ILCs were linked to CD8+ T cells with low expression of genes related to T cell activation and TCR signaling. Mass cytometry imaging further revealed that CD8+ T cells in direct contact with CD103+NKp46+ ILCs had lower expression of the cytotoxic molecule GZMB and the proliferation marker Ki67 compared to CD8+ T cells not in contact with these ILCs. Additionally, CD103+CD56+ ILCs inhibited autologous CD8+ T cells in vitro. Overall, our study identifies CD103+CD56+ inhibitory ILCs as being associated with dysfunctional CD8+ T cells within the tumor microenvironment of EOC. Further characterization of these inhibitory ILCs may provide novel therapeutic targets to enhance anti-tumor immune responses and improve clinical outcomes for patients with EOC. Funding Sources This work was supported by CIHR foundation award (CIHR FDN #143220), a TRANSCAN CIHR grant (CIHR – TRN #184713), a CHRYSALIDS TRANSCAN3 CCS grant, and a CCS grant (CCSRI # 706152) that was generously funded in memory Mr. Jim Jo Tak. This work was also supported by the Wolfund Immunotherapy Fund at the Princess Margaret Cancer Foundation, which was generously donated by the Wolfond Family. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)