Oncogenic Tyk2 mutations have been found in leukemias,29–34 and several cancer types such as squamous cell carcinoma and prostate cancer exhibit Tyk2 activation.35–37 However, loss-of-function (LOF) mutations have also been described in breast, gastric and colon cancer.38 In this study, we examined tumor cell-intrinsic and extrinsic functions of Tyk2 in CRC. This evidence concerns the gene TYK2 and squamous cell carcinoma.