LAG3 and neoplasm: More importantly, the TME of CRC can induce immune resistance through other multiple mechanisms, including the infiltration of immunosuppressive cells (Tregs, MDSC, TAMs), oncogenic signaling pathway-mediated immunosuppression (WNT/β-catenin, TGF-β, interferon-γ), tumor metabolism (lactic acid accumulation, hypoxia, glycolysis), overexpression of other suppressive immune checkpoints and molecules (LAG-3, TIM-3, IGIT), and gut microbiota (53–55).