Abstract 1354: Anti-CTLA-4 generates memory T-cells with greater expansion and functionality than anti-PD-1

Abstract

Abstract Distinct effects on T-cell differentiation arise from immune checkpoint inhibition targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1). However, the effect of these immunotherapies on the immunological memory response remains unclear. Our investigation into the effects of anti-CTLA-4 and anti-PD-1 on memory T-cell formation in mice revealed that anti-CTLA-4 generates a more effective memory antitumor response than anti-PD-1. Memory T-cells arising after anti-CTLA-4 treatment exhibit greater expansion, cytokine production, and antitumor activity than those from anti-PD-1. Notably, anti-CTLA-4 preserves more TCF-1+ T-cells during priming, while anti-PD-1 leads to more TOX+ T-cells. Experiments using conditional TCF-1- or TOX-knockout mice highlight TCF-1 is essential for memory response generated by anti-CTLA-4, whereas TOX deletion alone in T cells has no effect on response to anti-PD-1. Deepening our understanding of how checkpoint inhibition affects memory response is crucial for advancing our understanding of the enduring impacts 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-cells with greater expansion and functionality than anti-PD-1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1354.