Abstract B047: Tertiary lymphoid structures and B cells signatures determine clinically relevant T cell phenotype in ovarian cancer

Abstract

Abstract Tertiary lymphoid structures (TLSs) are ectopic lymphoid formations that arise at sites with persistent inflammatory conditions, including tumors. TLSs are composed predominantly of B cells, T cells, and CD21+ CD23+ follicular dendritic cells and exhibit different levels of the organization, ranging from locally concentrated aggregates of immune cells to well-defined B cell follicles to mature follicles with germinal center formation. Supporting key relevance for TLSs in natural and immunotherapy-driven immunosurveillance, intratumoral TLS density has been associated with improved disease outcome and response to cancer immunotherapy, mainly check-point inhibitors (ICIs) in solid carcinomas. Here, we demonstrate that compared to the immunologically hot tumors like non-small cell lung carcinoma (NSCLC), human high-grade serous ovarian carcinoma (HGSOC) contains only a limited number of TLS with germinal center formation. In parallel, TLS frequency and maturation positively correlate with progenitor stem-like CD8+ T cell phenotype. In line with this notion, B cell depletion in HGSOC biopsies promoted terminally exhausted, poorly ICI-sensitive CD8+ T cells, suggesting a critical role of intratumoral B cells in maintaining T cell effector functions. These findings point to key numerical and functional differences between mature TLSs in ICI-responsive vs ICI-irresponsive neoplasms that may guide the development of alternative ICI-based immunotherapies for patients with HGSOC. Citation Format: Irena Kusova Moserova, Lenka Kasikova, Jana Rakova, Jana Tomankova, Michal Henser, Tereza Lanickova, Katerina Mojzisova, Jana Drozenova, Jan Laco, Lukas Rob, Michael Halaska, Ales Ryska, Robert Lischke, Jiri Vachtenheim, David Cibula, Lorenzo Galluzzi, Radek Spisek, Jitka Fucikova. Tertiary lymphoid structures and B cells signatures determine clinically relevant T cell phenotype 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 B047.