Combined use of TLR4 and TLR7/8 agonists to improve the efficacy of immune checkpoint inhibitors in “hot” tumor treatment and the establishment of long-term immune protection

Abstract

Abstract Immunocheckpoint inhibitors, as an efficient cancer treatment, can only benefit some patients, so it is still necessary to find a better treatment strategy. As the strongest antigen presenting cell in human body, dendritic cells (DCs) play an important role in innate and adaptive immune response. Previous research has shown that the combination of toll-like receptor 4(TLR4) and toll-like receptor 7/8(TLR7/8) agonists can mutually stimulate DCs, thus they are being used in a mouse tumor model together with the recently discovered TNFR2 immune checkpoint inhibitor (ICI) to promote Th1 response and restrain immune tolerance in the tumor microenvironment. The findings indicate that triple therapy exhibits the capability to eliminate “hot” tumors, enhance the secretion of T cytokines, and enhance the migration and maturation of DCs, consequently leading to anti-tumor effects, as well as creating long-term tumor-specific protection. The ineffectiveness on “cold” tumors may be attributable to their low immunogenicity. This research simultaneously creates a fresh theoretical foundation for preclinical treatments of cancer.