Figure 3.

Next-generation PRR-based therapeutic approaches for cancer patients. PRR-targeting agonists, especially when combined with anti-inflammatory and/or immunostimulatory agents, can switch an immunosuppressive tumor microenvironment (TME) hostile for T cell trafficking and fitness toward an immunogenic milieu. PRR agonists promote MDSC maturation into inflammatory monocytes and granulocytes and increase the M1/M2 macrophage ratio. Combining PRR-targeting therapies with classic immunotherapy might support the establishment of TLSs containing a CD3⁺ T cell zone with mature dendritic cells (DCs) and a germinal center with B cells and follicular DCs. The coordinated actions of tumor antigen presentation through DCs and cytotoxic effector T cells and B cells enable the in situ priming and sustainment of antitumor adaptive immunity. MDSCs, myeloid-derived suppressor cells; DCs, dendritic cells; Treg, regulatory T cell; PRRs, pattern recognition receptors; TLR, Toll-like receptor; STING, stimulator of interferon genes; IFN, interferon; ICIs, immune checkpoint inhibitors; Arg1, arginase 1; iNOS, inducible nitric oxide synthase; IDO1, indoleamine 2,3-dioxygenase 1; PD1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; TLS, tertiary lymphoid structure; MHC, major histocompatibility complex; TCR, T cell receptor.