For TME cell infiltration (Fig. 4F), both adaptive and innate immune cells were enriched in gene-cluster C. Overall, based on necroptosis-related genes, there were two stable distinct phenotypes in CRC: like NRC1, gene-cluster A was characterized by few TME cells infiltration (Figs. 3F and 4D) but with EMT/ TGF-β pathways activation, and like NRC3, gene-cluster C was characterized by remarkable stromal, immune cells infiltration, and EMT/TGF-β activation, which was similar to CMS4-like and thus recognized as an immune-excluded phenotype[23]. The gene discussed is TGFB1; the disease is colorectal carcinoma.