Chronic Psychological Stress Attenuates the Efficacy of anti-PD-L1 Immunotherapy for Bladder Cancer in Immunocompetent Mice

Cancer Invest. 2021 Jul-Aug;39(6-7):571-581. doi: 10.1080/07357907.2021.1943746. Epub 2021 Jul 2.

Abstract

We aimed to explore whether chronic psychological stress affects the efficacy of immune checkpoint inhibitors (ICIs) immunotherapy in bladder cancer. The chronic unpredictable mild stress (CUMS) process was applied during the administration of anti-PD-L1 for subcutaneous tumors in mice. Tumor regression was obviously shown in anti-PD-L1 therapy groups, while this effect was notably attenuated by CUMS. Additionally, increased infiltration of regulatory T-cells, decreased amount of CD8+ lymphocytes, and reduced levels of tumor-associated cytokines in tumor sites were observed in mice treated with anti-PD-L1 under CUMS. Therefore, chronic psychological stress could weaken the potency of anti-PD-L1 immunotherapy for bladder cancer.

Keywords: Bladder cancer; PD-L1; chronic psychological stress; immunotherapy; tumor-infiltrating lymphocytes.

MeSH terms

  • Animals
  • B7-H1 Antigen / metabolism*
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage*
  • Immune Checkpoint Inhibitors / pharmacology
  • Immunocompetence
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Mice
  • Stress, Psychological / etiology
  • Stress, Psychological / immunology*
  • Treatment Outcome
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / immunology
  • Urinary Bladder Neoplasms / psychology
  • Xenograft Model Antitumor Assays

Substances

  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Cytokines
  • Immune Checkpoint Inhibitors