Abstract A009: CD103+CD56+ innate lymphoid cells are associated with an immunosuppressive microenvironment in ovarian cancer

Abstract

Abstract Background: Regulatory innate lymphoid cells (ILCregs) are an emerging heterogenous subset of innate lymphoid cells that suppress immunity in several healthy and diseased contexts, including cancer. Previously, we identified CD56+ ILCregs from in vitro expanded tumour-infiltrating lymphocyte (TIL) cultures in patients with epithelial ovarian carcinoma (EOC). However, lineage-defining surface markers or transcription factors that distinguishes these regulatory populations from other conventional NK cells have not been identified. The objective of this study is to characterize markers that define ILCregs directly from primary tumours and investigate its role within the tumour microenvironment (TME). Methods: Women with suspected abdominal mass were recruited and consented at Gynecology Cancer Clinic at Princess Margaret Hospital. Surgically resected EOC tumours were processed and analyzed by flow cytometry and single-cell RNA-sequencing. Suppression assays were performed by co-culture of tumour-infiltrating CD103+CD56+ ILCregs with autologous TILs for 4 days in vitro with soluble αCD3. Results: We found that CD103 expressing CD56+ ILCregs were associated with poor clinical prognosis in patients with ovarian carcinoma. CD103+CD56+ ILCregs displayed reduced expression of cytolytic related markers (i.e., GZMB, CD107a, CD16) compared to CD103-CD56+ NK cells and had a distinct transcriptomic profile from NK cells. Interestingly, CD103+CD56+ ILCregs displayed distinct surface markers (i.e., CD49a, CD69, GITR) and transcription factor networks that were associated with Treg development, differentiation, and suppressive function. Intratumoural CD103+CD56+ ILCregs suppressed autologous CD8+ T cells by downregulation of granzyme B in vitro. Concordantly, the abundance of CD103+CD56+ ILCregs in patient tumours were associated with reduced activated CD8+ T cells within the TME. Conclusion: This study identified CD103+CD56+ ILCregs in the TME of patients with EOC that are associated with poor clinical prognosis and plays a key role in regulating T cells. Further investigations into underlying immunoregulatory networks, including ILCregs, within the TME may provide novel targets to improve prognosis for patients with EOC. Citation Format: Douglas C Chung, Jehan Vakharia, Kathrin Warner, Nicolas Jacquelot, Azin Sayad, SeongJun Han, Maryam Ghaedi, Carlos R Garcia-Batres, Alisha Elford, Ben X Wang, Linh T Nguyen, Patricia A Shaw, Blaise A Clarke, Marcus Q Bernardini, Sarah E Ferguson, Pamela S Ohashi. CD103+CD56+ innate lymphoid cells are associated with an immunosuppressive microenvironment in ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A009.