Blockade of immune inhibitory receptors PD1 and CTLA-4 can reinvigorate anti-tumor T cells eliciting tumor regression and improved survival in melanoma and several other tumor types. However, just under half of all melanoma patients are resistant to these immune-based therapies. Researchers in the McQuade lab found melanoma patients on a fiber-rich diet are five times more likely to respond to anti-PD1 immunotherapy than patients on a low-fiber diet. Furthermore, patients on a fiber-rich diet had a greater abundance of gut bacteria known to be associated with ICB response and known to be involved in fiber metabolism. To determine if high-fiber diet intervention can increase systemic and anti-tumor immunity, the McQuade group has initiated a randomized, controlled trial in metastatic melanoma. Patients receiving anti-PD1 in either the adjuvant or unresectable setting will be randomized to a high-fiber diet or control diet, and both T cell activation and promotion of CD8 T cell memory will be assessed in the periphery and tumor microenvironment. Parallel studies in anti-PD1 treated, germ-free, melanoma tumor-bearing mice will be carried out using a fecal microbiota transplant (FMT) model. Mice will receive FMT from pre- and post-diet specimens obtained from melanoma patients in an ongoing fiber feeding study. Microbiome, immune profiling, and tumor growth rates will be compared across treatment groups to determine if post-dietary intervention FMT, through alteration of the microbiome, can enhance anti-PD1 efficacy. Confirmation of diet-enhanced anti-tumor immunity will support initiation of larger trials evaluating the impact of fiber-rich dietary intervention on immunotherapy outcomes.