The role of DCs in cancer therapies. (A) Tumor-cell deaths, induced by radiation therapy and chemotherapy, release various molecules activating or inhibiting immune responses of DCs in TME. As binding to TLR4, HMGB1 can elicit the activation of DCs. ATP binds to P2X7 receptor, triggering NLRP3 inflammasome and promoting IL-1β secretion. Tumor-derived DNA also induces a cGAS-STING pathway leading to DC activation. However, Trex1 suppresses the cGAS-STING pathway by degrading tumor-derived DNA. (B) DCs can increase the efficacy of adoptive T-cell therapy. CXCL9 and CXCL10 chemokines produced by DCs promote T-cell recruitment into tumor sites. CD40-CD40L interactions between DCs and T cells intensify the activation of T cells. (C) In terms of ICB therapy, IL-12 produced by DCs is required for PD-1 blockade. At the same time, DCs must sense IFN-r produced by T cells. Because improved DC functions can elevate the efficacy of ICB therapy, DC-activating adjuvants are combined with ICB, such as aCD40 antibody, poly I:C, FLT3-LG, and cGAMP.
