Table 5.

Characteristics of T cell exhaustion in cold tumors

Categories	Components	Mechanism	Refs.
T cell exhaustion	MDSCs	ARG-1 activation-mediated L-arginine deprivation	[238, 247]
		NOX and iNOS activation-mediated chemokine oxidation and TCR nitration	[248–250]
		Production of TGF-β and IL-10 and up-regulation of PD-L1	[245, 251, 252]
		Up-regulation of angiogenic factors (VEGF, bFGF, and PD-ECGF)	[253, 254]
		Activation of Tregs	[238, 241]
	TAMs	Expression of angiogenic factors (Wnt7b, TIE2, TP, and VEGF)	[255]
		Expression of PD-1 and CTLA-4 ligands	[261, 262]
		Up-regulation of TRAIL or Fas inducing T cell apoptosis	[261, 263]
		Secretion of cytokines (TGF-β and IL-10) for T cell inhibition	[264, 265]
		Release of chemokines (CCL5, CCL20, and CCL22) for Treg recruitment	[266, 267]
	Tregs	Secretion of cytokines (TGF-β and IL-10) for T cell inhibition	[271]
		IL-2 deprivation	[3]
		CD39/CD73-mediated adenosine generation	[3]
		CTLA-4 expression-mediated competition with CD28 for CD80/CD86 binding	[3]