Effects of Tryptophan Metabolites on Polarization of CD8+ Tfh-like T Cells

CD8+ cytotoxic T cells are critical to a successful anti-tumor response, but their different phenotypes have distinct functions and gene expression. Previous studies have demonstrated a connection between L-tryptophan metabolites and polarization of CD4+ T cell differentiation, with preliminary data from the Chang Lab showing markers characteristic of CXCR5+ CD4+ Tfh cells, as well as some indication that CXCR5+ CD8+ Tfh-like cells may also be induced by the metabolites. Continued investigation of this relationship could produce more effective and precise cancer treatments by engineering cell populations. In this study, we probe the connections between the L-tryptophan metabolic pathway, CD8+ Tfh-like cell differentiation, and the capacity of these cells to support melanoma tumor clearance. To this end, we further defined the capacity of L-Tryptophan metabolites in the promotion of CXCR5+ CD8+ T cell differentiation via in vitro treatment of CD8+ T cells with L-Tryptophan metabolites. Furthermore, the extent of potential anti-tumor functionality conferred by treatment of the cells was determined through challenge of melanoma in tumor-bearing mice.