Anti- CTLA-4 generates greater memory response than anti- PD-1 via TCF-1

• 成果类型: Article
• 署名作者: Mok, Stephen; Liu, Huey; Cobanoglu, Didem Agac; Anang, Nana- Ama A. S.; Mancuso, James J.; Wherry, E. John; Allison, James P.
• 署名单位: University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Pennsylvania; University of Texas System; UTMD Anderson Cancer Center
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14828
• DOI: 10.1073/pnas.2418985122
• 发表日期: 2025-01-14
• 关键词: regulatory t-cells; epigenetic landscape; anti-ctla-4 therapy; blockade; pembrolizumab; ipilimumab; effector; survival; efficacy; differentiation

摘要

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 reveals that memory T cells generated by anti- CTLA- 4 exhibit greater expansion, cytokine preserves more T cell factor- 1 (TCF- 1)+ T cells during priming, while anti- PD- 1 leads to using conditional Tcf7- or Tox- knockout mice highlight that TCF- 1 is essential for the memory response generated by anti- CTLA- 4, whereas TOX deletion alone in T cells has no effect on the 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.