Cancer immunotherapy has been widely recognized as a powerful approach to fight cancers. To date, over 50 phase III trials in cancer immunotherapy are in progress. Among the many immunotherapy approaches, immune checkpoint therapy has attracted considerable attention. The reported clinical success of targeting the T cell immune checkpoint receptors PD-1 or CTLA4 by antibodies blockade in advanced stages of cancers has demonstrated the importance of immune modulation. But antibodies-based immunotherapy confronted with some disadvantages, such as immunogenicity, stability, membrane permeability, and production cost. Therefore, alternative approaches including small-molecule-regulated immune response are being introduced. In this review, we focused on some of the key intracellular pathways where small-molecule therapeutic is potential and attractive, which highlights the great potential of natural products in this field.
Keywords: Cancer immunotherapy; IDO1; NKG2DL; PD(L)-1; STING; TLRs.