Table 2.

Immune cells involved in the liver immune microenvironment of CRLM

Immunological characteristics	Immune cells	Roles in CRLM
Immunosuppressive	Treg 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 Treg 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 Treg 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

PRF Perforin, GZM Granzyme, MMP Matrix metalloproteinase, AGR2 Anterior gradient-2