Targeting interleukin-17 enhances tumor response to immune checkpoint inhibitors in colorectal cancer

Although immune checkpoint inhibitors (ICIs) have gained much attention in managing cancer, only a minority of patients, especially those with tumors that have been classified as immunologically “cold” such as microsatellite stable (MSS) colorectal cancers (CRC), experience clinical benefit from ICIs. Surprisingly, interleukin-17 (IL-17) and its primary source Th17 are enriched in CRC and inversely associated with patient outcome. Our previous study revealed that IL-17A could upregulate programmed death-ligand 1 (PD-L1) expression and impede the efficacy of immunotherapy. IL-17, therefore, can be a possible target to sensitize tumor cells to ICIs. The detailed clinical results from our trial, which is the first to show the benefits of the combination of anti-PD-1 with anti-IL-17 therapy for MSS CRC, have also been presented. In this review, we highlight the role of IL-17 in ICIs resistance and summarize the current clinical evidence for the use of combination therapy. Directions for future strategies to warm up immunologically “cold” MSS CRCs have also been proposed.