Anti-CTLA-4 Generates Greater Memory Response Than Anti-PD-1 via TCF-1

Authors

Stephen Mok
Huey Liu
Didem Ağaç Çobanoğlu
Nana-Ama A S Anang
James J Mancuso
E John Wherry
James P Allison

Publication Date

1-14-2025

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abstract

The effects of T cell differentiation arising from immune checkpoint inhibition targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) on the immunological memory response remain unclear. Our investigation into the effects of anti-CTLA-4 and anti-PD-1 on memory T cell formation in mice reveals that memory T cells generated by anti-CTLA-4 exhibit greater expansion, cytokine production, and antitumor activity than those from anti-PD-1. Notably, anti-CTLA-4 preserves more T cell factor-1 (TCF-1)+ T cells during priming, while anti-PD-1 leads to more thymocyte selection-associated high mobility group box (TOX)+ T cells. Experiments using conditional

Keywords

Animals, Mice, Immunologic Memory, CTLA-4 Antigen, Programmed Cell Death 1 Receptor, Mice, Knockout, Hepatocyte Nuclear Factor 1-alpha, Immune Checkpoint Inhibitors, Memory T Cells, Mice, Inbred C57BL

DOI

10.1073/pnas.2418985122

PMID

39786926

PMCID

PMC11745370

PubMedCentral® Posted Date

1-9-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes