RET and neoplasm: Several reports showed that regorafenib modulated immuno-suppressive tumor microenvironment by blocking VEGFRs, TIE2, and CSF-1R, RET/Src axis signal pathways, and increased intratumoral CD45+ leukocytes, CD8+ T cells, which would enhance anti-tumor immunity when using regorafenib alone and plus various immunotherapies [19–21].