The interaction between tumor and the immune system is still poorly understood. Significant clinical responses have been achieved in cancer patients treated with antibodies against the CTLA4 and PD-1/PD-L1 checkpoints; however, only a small portion of patients responded to the therapies, indicating a need to explore additional co-inhibitory molecules for cancer treatment. B7-H3, a member of the B7 superfamily, was previously shown by us to inhibit T-cell activation and autoimmunity. In this study, we have analyzed the function of B7-H3 in tumor immunity. Expression of B7-H3 was found in multiple tumor lines, tumor-infiltrating dendritic cells, and macrophages. B7-H3-deficient mice or mice treated with an antagonistic antibody to B7-H3 showed reduced growth of multiple tumors, which depended on NK and CD8 T cells. With a putative receptor expressed by cytotoxic lymphocytes, B7-H3 inhibited their activation, and its deficiency resulted in increased cytotoxic lymphocyte function in tumor-bearing mice. Combining blockades of B7-H3 and PD-1 resulted in further enhanced therapeutic control of late-stage tumors. Taken together, our results indicate that the B7-H3 checkpoint may serve as a novel target for immunotherapy against cancer.

SummaryType 1 diabetes (T1D) is an autoimmune disease, which is characterized by the destruction of islet β cells in the pancreas triggered by genetic and environmental factors. In past decades, extensive familial and genome‐wide association studies have revealed more than 50 risk loci in the genome. However, genetic susceptibility cannot explain the increased incidence of T1D worldwide, which is very likely attributed by the growing impact of environmental factors, especially gut microbiome. Recently, the role of gut microbiome in the pathogenesis of T1D has been uncovered by the increasing evidence from both human subjects and animal models, strongly indicating that gut microbiome might be a pivotal hub of T1D‐triggering factors, especially environmental factors. In this review, we summarize the current aetiological and mechanism studies of gut microbiome in T1D. A better understanding of the role of gut microbiome in T1D may provide us with powerful prognostic and therapeutic tools in the near future.