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

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
• chronic psychological stress
• PD-L1
• immunotherapy
• tumor-infiltrating lymphocytes

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

This work was funded by the Natural Science Foundation of China [NSFC, no.81372756], and Science and Technology Commission of Shanghai Municipality [no. 19ZR1408000].