Previously, IL-22 was shown to induce OLFM4 in colon adenocarcinoma cell lines29; however, the opposite effects have also been reported, with IL-22 dampening the expression of LGR5 and OLFM4 in murine small bowel organoids.34, 35 Moreover, Th22 cells can promote CRC through the activation of STAT3 and induction of the DOT1L complex, which regulates the expression of stem cell–associated genes, such as NANOG, SOX2, and POU5F1.36 However, in our study, NANOG and POU5F1 were not significantly affected by IL-22 stimulation. Here, DOT1L is linked to colon adenocarcinoma.