The chemical biology of IL-12 production the non-canonical NFkB pathway.

Interleukin-12 (IL-12) has emerged as an attractive cytokine for cancer therapy because it has direct anti-cancer effects and additionally plays a critical role in enhancing checkpoint inhibitors. Given these multiple modes of actions, identifying means to pharmacologically induce IL-12 production in the tumor microenvironment has become important. In this review, we highlight therapeutics that promote IL-12 induction in tumor-associated myeloid cells through the non-canonical NFkB pathway. We discuss existing clinical trials and briefly examine the additional pathway targets that warrant further exploration for drug discovery.