Anti oxidative Amino Acid L ergothioneine Modulates the Tumor Microenvironment to Facilitate Adjuvant Vaccine Immunotherapy
Cancer vaccines consist of a tumor associated antigen (TAA) and adjuvant. These vaccines induce and activate proliferation of TAA specific cytotoxic T lymphocytes (CTLs) suppressing tumor growth. The therapeutic efficacy of TAA specific CTLs depends on the properties of tumor microenvironment. The environments make immunosuppressive by function of regulatory T cells and tumor associated myeloid cells; thus, regulation of these cells is important for successful cancer immunotherapy. We report here that L ergothioneine (EGT) with the adjuvant Toll like receptor 2 (TLR2) ligand modulated suppressive microenvironments to be immune enhancing. EGT did not augment DC mediated CTL priming or affect CTL activation in draining lymph node and spleen. However, EGT decreased the immuno suppressive function of tumor associated macrophages (TAMs) TLR2 stimulation accompanied with EGT administration downregulated expression of PD L1, CSF 1R, arginase 1, FAS ligand, and TRAIL in TAMs, reflecting reduction of CTL suppression. An anti oxidative thiol thione residue of EGT was essential to dampening CTL suppression. The effect was specific to the thiol thione residue of EGT because no effect was observed with another anti oxidant N acetyl L cysteine (NAC) A CTL suppressive environment made by TLR2 is relieved to be improved by the addition of EGT, which may ameliorate the efficacy of vaccine immunotherapy.
Front. Immunol.