This is exemplified by foundational studies showing that CTLA-4 blockade efficacy in melanoma is microbiota-dependent: germ-free mice fail to respond to anti-CTLA-4, but oral supplementation with Bacteroides thetaiotaomicron or B. fragilis restores responsiveness by inducing intratumoral T cell infiltration and Th1 cytokine production (253). This evidence concerns the gene CTLA4 and melanoma.