Table 1.

Factors that contribute to immunosuppression in the TME of CRC.

Classes	Immunosuppressors	Major Immune Cells Affected	References
Cell surface protein	PD-1	T cell, NK cell, TAM, DC	[45,46,47,48,49]
	TIGIT	T cell, NK cell	[50,51]
	TGFβ RII	Treg	[52,53,54,55]
	GARP	CD4+ and CD8+ T cells	[56]
	CD39	NK cell	[57]
	CD73	Effector T cell	[58]
	A2A adenosine receptors	T cell	[57]
	CCR8	Treg	[59,60]
	Disrupted Immunosurveillance Contributors	Major Immune Cells Affected	References
	NKG2D receptor	NK cell	[61,62]
	TLRs	Innate immune cell	[63]
	CD80	T cell	[64]
Cytokines/Chemokines	Immunosuppressors	Major Immune Cells Affected	References
	TGFβ	Treg	[65]
	VEGF	T cell, MDSC, DC	[66,67]
	IL-6	CD4+ and CD8+ T cells	[68,69]
	CXCL3 and CXCL4	Treg, CD8+ T cell	[70,71]
	HMGB1	PMDDC	[72]
	Disrupted Immune Activators	Major Immune Cells Affected	References
	IL-12	NK cell, T cell	[73]
	IL-15	NK cell, CD8+ T cell	[74]
	IL-24	CD4+ and CD8+ T cells	[75,76,77]
	CXCL9, CXCL10, and CXCL11	CD4+ and CD8+ T cells	[78,79,80]
Phosphatase	Immunosuppressor	Major Immune Cells Affected	References
	SHP2	CD4+ and CD8+ T cells	[81,82,83]
Transcriptional factors	Immunosuppressors	Major Immune Cells Affected	References
	PRC2	Th1 and CD8+ T cells	[84]
	FOXM1	BMDC	[85]
	NF-κB	DC	[86]
	STAT1	CD4+ T cell	[83]
	STAT3	CD4+ T cell, DC	[82,87]
	TRF2	NK cell	[88]
Metabolic enzymes	Immunosuppressors	Major Immune Cells Affected	References
	ODC	M1 macrophage	[20,89]
	IDO1	CD4+ and CD8+ T cells, NK cell, MDSC	[90,91]
Other factors	Immunosuppressive factors	Major Immune Cells Affected	References
	Extracellular adenosine level	T cell	[57,58]
	Hypoxia	Treg, CD4+ effector T cell, MDSC, TAM, DC	[92,93]

Abbreviations: dendritic cell, DC; tyrosine-based inhibitory motif domain, TIGIT; high mobility group box-1, HMGB1; peritoneal macrophage-derived dendritic cells, PMDDC; ornithine decarboxylase, ODC.