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

Overview

abstract

  • 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

  • CD8-Positive T-Lymphocytes
  • Immune Tolerance
  • Lymphocytes, Tumor-Infiltrating
  • Neoplasms
  • Potassium
  • Stem Cells

Identity

PubMed Central ID

  • PMC8194369

Scopus Document Identifier

  • 85064134700

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2018.08.040

PubMed ID

  • 30923193

Additional Document Info

volume

  • 363

issue

  • 6434