Cytokine and Chemokine Signals of T-Cell Exclusion in Tumors

Front Immunol. 2020 Dec 14:11:594609. doi: 10.3389/fimmu.2020.594609. eCollection 2020.

Abstract

The success of cancer immunotherapy in solid tumors depends on a sufficient distribution of effector T cells into malignant lesions. However, immune-cold tumors utilize many T-cell exclusion mechanisms to resist immunotherapy. T cells have to go through three steps to fight against tumors: trafficking to the tumor core, surviving and expanding, and maintaining the memory phenotype for long-lasting responses. Cytokines and chemokines play critical roles in modulating the recruitment of T cells and the overall cellular compositions of the tumor microenvironment. Manipulating the cytokine or chemokine environment has brought success in preclinical models and early-stage clinical trials. However, depending on the immune context, the same cytokine or chemokine signals may exhibit either antitumor or protumor activities and induce unwanted side effects. Therefore, a comprehensive understanding of the cytokine and chemokine signals is the premise of overcoming T-cell exclusion for effective and innovative anti-cancer therapies.

Keywords: T-cell exclusion; cell therapy; chemokine; cytokine; immunotherapy.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Chemokines / immunology*
  • Humans
  • Neoplasm Proteins / immunology*
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology

Substances

  • Chemokines
  • Neoplasm Proteins