To better understand the impact of DNA methylation on immune dysfunction and potential resistance to immune-based therapy in CRC patients, we integrated data from TCGA with cutting edge bioinformatic techniques demonstrating that, in CMS1 patients, the “inflamed” subtype of CRC, TBX21 methylation, and expression stratified patients into groups with significantly different survival. The gene discussed is TBX21; the disease is colorectal carcinoma.