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

Highlights d Novel mouse system to uncouple tumor mutational load and tumor heterogeneity d Lower tumor heterogeneity leads to decreased tumor growth because of immune rejection d Both clone numbers and their genetic diversity mediate tumor growth and rejection d Tumor heterogeneity is linked to patient survival and checkpoint blockade response

TGFβ is over expressed in advanced human cancers. It correlates with metastasis and poor prognosis. However, TGFβ functions as both a tumor suppressor and a tumor promoter. Here we report for the first time that genetic deletion of Tgfbr2 specifically in myeloid cells (Tgfbr2MyeKO) significantly inhibited tumor metastasis. Reconstitution of tumor-bearing mice with Tgfbr2MyeKO bone marrow recapitulates the inhibited metastasis phenotype. This effect is mediated through decreased production of type 2 cytokines, TGFβ1, arginase 1 and iNOS, which promoted IFN-γ production and improved systemic immunity. Depletion of CD8 T cells diminished metastasis defect in the Tgfbr2MyeKO mice. Consistent with animal studies, myeloid cells from advanced stage cancer patients demonstrated an increased TGFβ receptor II expression. Our studies demonstrate that myeloid-specific TGFβ signaling is an essential component of the metastasis-promoting puzzle of TGFβ. This is in contrast to the previously reported tumor-suppressing phenotypes in fibroblasts, epithelial or T cells.