PD-1/PD-L1 and DNA Damage Response in Cancer

Cells. 2023 Feb 7;12(4):530. doi: 10.3390/cells12040530.

Abstract

The application of immunotherapy for cancer treatment is rapidly becoming more widespread. Immunotherapeutic agents are frequently combined with various types of treatments to obtain a more durable antitumor clinical response in patients who have developed resistance to monotherapy. Chemotherapeutic drugs that induce DNA damage and trigger DNA damage response (DDR) frequently induce an increase in the expression of the programmed death ligand-1 (PD-L1) that can be employed by cancer cells to avoid immune surveillance. PD-L1 exposed on cancer cells can in turn be targeted to re-establish the immune-reactive tumor microenvironment, which ultimately increases the tumor's susceptibility to combined therapies. Here we review the recent advances in how the DDR regulates PD-L1 expression and point out the effect of etoposide, irinotecan, and platinum compounds on the anti-tumor immune response.

Keywords: DNA damage response; cytotoxic drugs; immunotherapy; programmed death ligand-1 (PD-L1).

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • B7-H1 Antigen / metabolism
  • DNA Damage
  • Humans
  • Neoplasms* / drug therapy
  • Programmed Cell Death 1 Receptor* / metabolism
  • Tumor Microenvironment

Substances

  • Programmed Cell Death 1 Receptor
  • B7-H1 Antigen
  • Antibodies, Monoclonal

Grants and funding

This research received no external funding.