TGFB1 and colorectal carcinoma: The immune cells in the TIME regulating CRC development are achieved by the secreted immune molecules and CRC cell-surface receptors, activating the intracellular signaling pathways involving macrophages, including Wnt/β-catenin, NF-κB, PI3K/AKT, JAK/STAT3, MAPK, and TGF-β/Smad signaling pathways (Figure 2).