Selective inhibition of low-affinity memory CD8+ T cells by corticosteroids. Academic Article uri icon

Overview

abstract

  • Patients treated with immune checkpoint blockade (ICB) sometimes experience immune-related adverse events (irAEs), requiring immuno-suppressive drugs such as corticosteroids despite the possibility that immunosuppression may impair the antitumor effects of ICB. Here, we address the dilemma of using corticosteroids for the treatment of irAEs induced by ICB. ICB augments neoantigen-specific CD8+ T cell responses, resulting in tumor regression. In our model, simultaneous, but not late, administration of corticosteroids impaired antitumor responses with reduction of CD8+ T cell proliferation. Secondary challenge using tumors with/without the neoantigen showed selective progression in tumors lacking the neoantigen when corticosteroids were administered. Corticosteroids decreased low- but not high-affinity memory T cells by suppressing fatty acid metabolism essential for memory T cells. In a small cohort of human melanoma patients, overall survival was shorter after treatment with CTLA-4 blockade in patients who received early corticosteroids or had low tumor mutation burden. Together, low-affinity memory T cells are dominantly suppressed by corticosteroids, necessitating careful and thoughtful corticosteroid use.

publication date

  • September 19, 2019

Research

keywords

  • Adrenal Cortex Hormones
  • CD8-Positive T-Lymphocytes
  • Immunologic Memory
  • Immunosuppressive Agents

Identity

PubMed Central ID

  • PMC6888983

Scopus Document Identifier

  • 85075956675

Digital Object Identifier (DOI)

  • 10.1084/jem.20190738

PubMed ID

  • 31537643

Additional Document Info

volume

  • 216

issue

  • 12