We hypothesize that, in a subgroup of CRC patients, HDAC2 mutations reorganize immune-related genes via a mechanism involving CIITA, the mutation of which, in turn, drives the expression levels of MHC class II in cancer cells; this is followed by the stimulation of both CD4+ Th1 and Th2 helper cells, which are involved in cell-mediated and humoral immune response, respectively. This evidence concerns the gene HDAC2 and colorectal carcinoma.