Turning tumors into vaccines: co-opting the innate immune system

Immunotherapy of cancer must be effective in the pre-established disease; i.e., in the therapeutic rather than prophylactic setting. Here, we review novel immunotherapeutic approaches for targeting established cancers. In addition to novel checkpoint-blocking antibodies, recent insight into innate immune sensors may further improve cancer immunotherapy protocols and help to overcome the limitations of conventional therapeutic immunization strategies. Specifically, the local induction of IL-12 and IFNα turns the immunosuppressive tumor microenvironment into an immunosupportive tissue, which is attained, for example, by local Toll-like receptor or RIG-I-like receptor triggering. Notably, the latter are endogenously expressed in all tumor cells and have the advantage of turning tumors into tumor vaccines by inducing apoptosis and improving antigen presentation. Thus, immunostimulatory agents embody strong promise as a part of combinatorial cancer immunotherapies.