T cell stemness and dysfunction in tumors are triggered by a common mechanism Academic Article uri icon

Overview

MeSH Major

  • Arthrography
  • Glucocorticoids
  • Sacroiliac Joint
  • Triamcinolone Acetonide

abstract

  • 2017 © The Authors, some rights reserved. A paradox of tumor immunology is that tumor-infiltrating lymphocytes are dysfunctional in situ, yet are capable of stem cell–like behavior including self-renewal, expansion, and multipotency, resulting in the eradication of large metastatic tumors. We find that the overabundance of potassium in the tumor microenvironment underlies this dichotomy, triggering suppression of T cell effector function while preserving stemness. High levels of extracellular potassium constrain T cell effector programs by limiting nutrient uptake, thereby inducing autophagy and reduction of histone acetylation at effector and exhaustion loci, which in turn produces CD8 + T cells with improved in vivo persistence, multipotency, and tumor clearance. This mechanistic knowledge advances our understanding of T cell dysfunction and may lead to novel approaches that enable the development of enhanced T cell strategies for cancer immunotherapy.

publication date

  • March 29, 2019

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1126/science.aau0135

PubMed ID

  • 30923193

Additional Document Info

volume

  • 363

number

  • 6434