Interplay between inflammasomes and PD-1/PD-L1 and their implications in cancer immunotherapy

Abstract

Abstract The inflammasomes play crucial roles in inflammation and cancer development, while the PD-1/PD-L1 pathway is critical for immune suppression in the tumor microenvironment (TME). Recent research indicates a reciprocal regulatory relationship between inflammasomes and PD-1/PD-L1 signaling in cancer development and PD-1 blockade treatment. By activating in diverse cells in tumor tissues, inflammasome upregulates PD-L1 level in the TME. Moreover, the regulation of PD-1/PD-L1 activity by inflammasome activation involves natural killer cells, tumor-associated macrophages and myeloid-derived suppressor cells. Conversely, PD-1 blockade can activate the inflammasome, potentially influencing treatment outcomes. The interplay between inflammasomes and PD-1/PD-L1 has profound and intricate effects on cancer development and treatment. In this review, we discuss the crosstalk between inflammasomes and PD-1/PD-L1 in cancers, exploring their implications for tumorigenesis, metastasis and immune checkpoint inhibitor (ICI) resistance. The combined therapeutic strategies targeting both inflammasomes and checkpoint molecules hold promising potential as treatments for cancer.