Differential regulation of the response to radiation therapy by commensal bacteria and fungi

The intestinal microbiome, typically equated with bacteria, influences the response to chemotherapy and immunotherapy in multiple cancer types. Here, we show that intestinal commensal fungi regulate the anti-tumor immune response following radiation and that fungi have an inverse relationship with bacteria in governing the response of tumors to radiation. Mice lacking commensal fungi show enhanced responsiveness to radiation, whereas mice without commensal bacteria exhibited reduced responses with associated overgrowth of commensal fungi. Mice devoid of intestinal fungi had increased intratumoral cytotoxic T cells and a reduction in suppressive T cells and macrophages. Thus, optimal responses to cancer therapies depend on the previously unrecognized commensal fungal population that mediates its effects by modulating the immunosuppressive functions of immune cells in the tumor microenvironment.