Consistent with our findings, a previous study indicated that supplementation with NAD+ inhibited CD8+ TIL function.(42) The other cold metabolites, taurolithocholate 3-sulfate and glycolithocholate sulfate, are derivatives of secondary bile acids, whose functions in antagonizing CTL-mediated tumor cell killing were recently identified in colorectal cancer.(43) The cold metabolites also include sex hormone precursors DHEA-S and androstenediol (3beta,17beta) disulfate (2), which could be converted to testosterone and/or estrogen. The gene discussed is PLXNA3; the disease is colorectal cancer.