Table 2 Immune cells involved in the liver immune microenvironment of CRLM

Immunosuppressive

T_reg cells

Inhibit effective responses of effector T cells and contribute to immune evasion of CRC

M2 macrophages

Secret cytokines including IL-10, TGF-β, CCL17 and CCL22 to induce the formation of an immunosuppressive TME; attenuate Th1 adaptive immunity; produce MMPs to regulate matrix remodelling

MDSCs

Induce the production of T_reg cells and repress the function of effective NK cells; produce MMP-9 and VEGF to promote TME remodelling and angiogenesis

TANs

Recruit M2 macrophages and T_reg cells to shape a suppressive TME in the liver; produce MMP-9 and neutrophil elastase to promote extravasation of CRC cells; form NETs to trap and facilitate the implantation of CRC cells to the liver; produce AGR2 to communicate with CRC cells to drive CRLM

Immuno-effective

CD4⁺ Th1 cells

Produce IFNγ and TNF-α, leading to cell-mediated killing

CD4⁺ Th2 cells

Secrete IL-4, which assists in the activation of humoral immunity

CD8⁺ T cells

Secret cytotoxic granules and release proteins to kill disseminated CRC cells; produce TNF-α, IL-2 and IFNγ to strengthen the cytotoxicity

M1 macrophages

Kill cancer cells directly by releasing cytotoxic reactive oxygen species (ROS), NO and IL-12

NKs

Release IFNγ and NO toupregulate the expression of functional Fas in CRC cells; exert cytotoxic effects to eliminate CRC cells by PRF and GZM and kill CRC cells directly by releasing the apoptosis-inducing ligand and FasL

DCs

Present antigens and deliver co-stimulatory signals for T-cell activation to initiate effective immune responses

TANs

Activate T-cell immune reaction by presenting antigens; release IL-18 to induce the activation of NK cells