These include both direct tumoricidal activities on cancer cells and indirect immunomodulatory effects on different immune cell subsets as well as other relevant cell types in the tumor microenvironment (TME) via on-target inhibition of BTK (for both drugs) or off-target inhibition of ITK or EGFR (for ibrutinib) (2, 24, 28, 29). This evidence concerns the gene BTK and cancer.