Abstract A054: Anti-CTLA-4 generates memory T-cell with greater expansion and functionality than anti-PD-1

Abstract

Abstract Blocking either cytotoxic T-lymphocyte antigen-4 (CTLA-4) or programmed cell death-1 (PD-1) pathway results in distinct T-cell differentiation. We investigated the effects of anti-CTLA-4 and anti-PD-1 on memory T-cell formation in mice. Anti-CTLA-4 generates a more potent memory response than anti-PD-1. Memory T-cells generated by anti-CTLA-4 expand at a greater frequency, have greater cytokine production, and exhibit higher antitumor activity than those generated by anti-PD-1. These memory cells also more frequently differentiate into KLRG1+ effector CD8 T-cells during re-challenge. Additionally, anti-CTLA-4 generates more TCF-1+ memory-like T-cells, while anti-PD-1 results in more TOX+ terminally differentiated T-cells. Together, we provide insights into the long-term effects of these immunotherapies on the immune system. Citation Format: Stephen Mok, Huey Liu, Nana-Ama A.S. Anang, James J Mancuso, Didem Ağaç Çobanoğlu, James P Allison. Anti-CTLA-4 generates memory T-cell with greater expansion and functionality than anti-PD-1 [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 A054.