Inosine modulates antitumor immunity: Checkpoint blockade immunotherapy harnesses the immune system to kill cancer cells and has been used with great success to treat certain tumors, but not all cancer patients respond. The efficacy of checkpoint blockade immunotherapy has been shown to depend on the presence of distinct, beneficial bacteria residing in the gut of patients, but how the microbiome mediates such beneficial effects is unclear. Mager et al. found that specific bacteria produce a metabolite called inosine that enhances the effect of checkpoint blockade immunotherapy (see the Perspective by Shaikh and Sears). In mouse models, inosine, together with proinflammatory stimuli and immunotherapy, strongly enhanced the antitumor capacities of T cells in multiple tumor types, including colorectal cancer, bladder cancer, and melanoma. Science , this issue p. 1481 ; see also p. 1427

Human glioblastomas harbour a subpopulation of glioblastoma stem cells that drive tumorigenesis. However, the origin of intratumoural functional heterogeneity between glioblastoma cells remains poorly understood. Here we study the clonal evolution of barcoded glioblastoma cells in an unbiased way following serial xenotransplantation to define their individual fate behaviours. Independent of an evolving mutational signature, we show that the growth of glioblastoma clones in vivo is consistent with a remarkably neutral process involving a conserved proliferative hierarchy rooted in glioblastoma stem cells. In this model, slow-cycling stem-like cells give rise to a more rapidly cycling progenitor population with extensive self-maintenance capacity, which in turn generates non-proliferative cells. We also identify rare ‘outlier’ clones that deviate from these dynamics, and further show that chemotherapy facilitates the expansion of pre-existing drug-resistant glioblastoma stem cells. Finally, we show that functionally distinct glioblastoma stem cells can be separately targeted using epigenetic compounds, suggesting new avenues for glioblastoma-targeted therapy.