SETD2 mutations are widespread in many tumor types, and the role of SETD2 in multiple tumors, including pancreatic tumor, has been explored.[8, 19] However, no small molecules or antibodies have shown specific targeted therapeutic potential for SETD2 and/or H3K36me3 loss.[20] Understanding how SETD2‐H3K36me3 loss reprograms the TME might provide an alternative strategy for targeting SETD2‐deficient/low tumors. Here, SETD2 is linked to neoplasm.