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Another benefit of dietary fiber The gut microbiome can modulate the immune system and influence the therapeutic response of cancer patients, yet the mechanisms underlying the effects of microbiota are presently unclear. Spencer et al . add to our understanding of how dietary habits affect microbiota and clinical outcomes to immunotherapy. In an observational study, the researchers found that melanoma patients reporting high fiber (prebiotic) consumption had a better response to checkpoint inhibitor immunotherapy compared with those patients reporting a low-fiber diet. The most marked benefit was observed for those patients reporting a combination of high fiber consumption and no use of over-the-counter probiotic supplements. These findings provide early insights as to how diet-related factors may influence the immune response. —PNK

Author Contributions G.M. designed and performed the experiments, analyzed and interpreted the data, and wrote the manuscript. M.A.M. designed and supervised the research, analyzed and interpreted the data, and wrote the manuscript. C.V.C. co-designed and assisted with high spatiotemporal resolution microscopy experiments. E.J.H. and J.R.P. co-designed and assisted with zebrafish experiments. N.M. and T.P. co-designed and performed the BBB-on-a-chip experiments. C.C.D. assisted with some of the experiments. L.I.Z. and D.E.I. provided zebrafish and BBB-on-a-chip models, respectively.

Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical bene t across tumor types, but a high rate of immune-related adverse events (irAE). Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we pro led the blood, tumor and gut microbiome of 77 advanced melanoma patients treated with CICB, with a high rate of any ≥Grade 3 irAEs (49%) with parallel studies in pre-clinical models. Tumor-associated immune and genomic biomarkers of response to CICB were similar to those identi ed for ICB monotherapy, and toxicity from CICB was associated with a more diverse peripheral T cell repertoire.Pro ling of gut microbiota demonstrated a signi cantly higher abundance of Bacteroides intestinalis in patients with toxicity, with upregulation of mucosal IL-1b in patient samples of colitis and in pre-clinical models. Together, these data offer potential new therapeutic angles for targeting toxicity to CICB. Main TextTreatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical bene t across tumor types, but a high rate of immune-related adverse events (irAE). Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we pro led the blood, tumor and gut microbiome of 77 advanced melanoma patients treated with CICB, with a high rate of any ≥Grade 3 irAEs (49%) with parallel studies in pre-clinical models. Tumor-associated immune and genomic biomarkers of response to CICB were similar to those identi ed for ICB