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

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.

Automated summary

The application of immunotherapy for cancer treatment is expanding rapidly. Combining immunotherapeutic agents with different treatments can enhance the clinical response in patients who have developed resistance to monotherapy. Chemotherapeutic drugs that induce DNA damage often increase the expression of PD-L1, which can be used by cancer cells to evade immune surveillance. Targeting PD-L1 on cancer cells can restore the immune-reactive tumor microenvironment, making the tumor more susceptible to combined therapies. This review discusses the recent advances in understanding how DDR regulates PD-L1 expression and the impact of certain chemotherapeutic drugs on the anti-tumor immune response.