Abstract 1343: CD8+ resident memory T (TRM) cells in tumors

Abstract

Abstract Tumor-resident memory T (TRM) cells play an important role in cancer diseases. Accumulating evidence indicates that subpopulations of CD3+CD8+ tumor-infiltrating lymphocytes (TIL) are TRM cells, and are emerging as activated tumor-specific T cells. These TRM cells are characterized by expression of CD103 integrin and identify tumor-reactive cytotoxic T lymphocytes (CTL). Human lung tumor CD103+CD8+ TRM cells co-express CD49a and CD69, and are associated with a favorable prognosis. They also express a panel of T-cell inhibitory receptors, including PD-1, and are able to kill autologous tumor cells upon blockade of PD-1 with neutralizing antibodies. This CD103+CD8+ TRM subset also emerges as a predictive biomarker of response to PD-1 blockade and expands during anti-PD-1 treatment in responder, but not in non-responder lung cancer patients. It is now widely admitted that expression of CD103 on activated CD8+ T lymphocytes and persistence of TRM cells in epithelial tissues requires transforming growth factor (TGF)-β. This cytokine is secreted in the tumor microenvironment in its inactive form bound to latency-associated protein (LAP), and is activated by αV integrins on tumor cells and immune cells. Using multiplex immunofluorescence staining on cohorts of anti-PD-(L)1-treated lung cancer patients, we recently showed that decreased expression of tumor αV is associated with improved immunotherapy-related-progression-free survival (PFS) and correlates with an increased density of CD8+CD103+ TIL. Cancer cell αV activates autocrine TGF-β and participates in inducing CD103 on activated CD8+ T cells. Our more recent studies in mouse tumor models and human cancers demonstrate that different CD8+ TRM subsets participate to response different immune checkpoint inhibitors and therapeutic cancer vaccines. Citation Format: Fathia Mami-Chouaib. CD8+ resident memory T (TRM) cells in tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1343.