These results are consistent with previous reports that TDLNs are necessary for the efficacy of immunotherapy in peripheral tumors.44–46 Taken together, these findings underscore the importance of the MLV-CLN network in regulation of RT-modulated anti-tumor responses and suggest a working model that RT stimulates the trafficking of brain tumor-derived DCs to CLNs and the subsequent activation of CD8+ T cells, which rely on intact MLVs (Fig. 7d). This evidence concerns the gene CD8A and brain neoplasm.