Targeting PARP1 to Enhance Anticancer Checkpoint Immunotherapy Response: Rationale and Clinical Implications

Reinvigorating the antitumor immune response using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of several malignancies. However, extended use of ICIs has resulted in a cancer-specific response. In tumors considered to be less immunogenic, the response rates were low or null. To overcome resistance and improve the beneficial effects of ICIs, novel strategies focused on ICI-combined therapies have been tested. In particular, poly ADP-ribose polymerase inhibitors (PARPi) are a class of agents with potential for ICI combined therapy. PARPi impairs single-strand break DNA repair; this mechanism involves synthetic lethality in tumor cells with deficient homologous recombination. More recently, novel evidence indicated that PAPRi has the potential to modulate the antitumor immune response by activating antigen-presenting cells, infiltrating effector lymphocytes, and upregulating programmed death ligand-1 in tumors. This review covers the current advances in the immune effects of PARPi, explores the potential rationale for combined therapy with ICIs, and discusses ongoing clinical trials.

Automated summary

The use of immune checkpoint inhibitors (ICIs) in cancer treatment has revolutionized the field, but prolonged use of ICIs has resulted in a specific response to certain types of cancer. To overcome resistance and improve outcomes, researchers have explored novel strategies involving the combination of ICIs with other therapies. One promising class of agents is poly ADP-ribose polymerase inhibitors (PARPi), which have the potential to enhance the antitumor immune response through various mechanisms.