Interestingly, the more abundant clones in MSH2 KO tumors (183, 187) overexpress BHLHE40, a tissue-specific regulator of murine tissue-resident macrophage proliferation 28, repressing IL-10 and increasing IFN-γ secretion, also involved in Th1-like cell and CD8+ memory T cell responses to CD40 agonist immunotherapy in CRC 29. Here, CD40 is linked to colorectal carcinoma.