Table 1.

The potential mechanisms of immune resistance.

Type		Mechanisms	Examples
Intrinsic mechanisms	Adaptive resistance	Activation of signaling pathways	PI3K WNT/β-catenin IFN-γ
		Upregulation of constitutive PD-L1 expression
		Epigenetic variations	KDM5B
		Loss of tumor antigen expression	Low mutation burden
	Acquired resistance
		Downregulation of tumor antigen presentation	The function defects of: Proteasome subunits transporters MHC itself β-2-microglobulin (B2M)
		Changes of T cells functional phenotype
		The mutations of tumor cells	JAK1/JAK2 B2M
Extrinsic mechanisms		Inhibitory immune checkpoints	CTLA-4 PD-1 LAG-3 VISTA
		T cell exhaustion and phenotypic changes
		immunosuppressive cells	TAMs Tregs
		The release of cytokine and metabolite	CSF-1 Adenosine tryptophan metabolites