Table 3.

Characteristics of T cell exclusion in cold tumors

Categories	Components	Mechanism	Refs.
Blockade of T cell infiltration	Down-regulation of T cell homing factors	Histone modifications and DNA methylation down-regulating CXCL9 and CXCL10	[154, 155]
		IDH-1/2-mediated R-2-hydroxyglutatate generation inhibiting CXCL9 and CXCL10 production	[156]
		CXCL9 and CXCL10 down-regulation due to reduced type I IFN	[157]
	Physical barriers	Release of mitogenic and fibrogenic factors (VEGF, PDGF, TGF-β, and SHH) for TAF activation owing to KRAS or NF-κB mutations	[161–164]
		Positive feedback network of pro-inflammatory cytokines (VEGF and TGF-β) for ECM deposition	[165]
		Abundant ECM components (collagens, glycoproteins, elastin, and hyaluronan)	[165]
	Hypoxia	VEGF resulting from HIF-1α up-regulation inducing FasL/Fas-mediated T cell apoptosis	[166, 167]
		High VEGF-mediated increase in neovascular permeability inducing plasma protein extravasation for facilitating ECM deposition	[158, 168]
		VEGF expression-mediated defects in leukocyte adhesion molecules (ICAM-1/2, VCAM-1, and CD34)	[169]