CD28 and colorectal carcinoma: Immunologic signature analysis was further carried out and showed that the upregulated mRNAs in CRC tumorigenesis were associated with alternatively activated M2 macrophages versus c-MYC inhibited and Th17 polarized CD4 T cells (Figure 4E), while downregulated mRNAs in CRC tumorigenesis were associated with genes downregulated in CD8 T cells activated by CD3/CD28 versus those stimulated by IFNAS, the transcription kinetics initiated by IL-4 in early differentiation of Th2 CD4+T cells, and genes downregulated in plasmacytoid dendritic cells (Figure 4F).