Table 1.

Effects of the tumor metabolism on TILs.

Metabolic alteration	Species	Inhibition	Promotion	Reference
Hypoxia	Mus musculus	Expansion of CD8+ T cells	Development of more lytic CTLs	Caldwell et al. (92 )
		IL2 and IFNγ production by CD8+ and CD4+ T cells	VEGF production
			Expression of TCR and LFA-1 on CD8+ T cells
	Human	Voltage-dependent K+ channels		Conforti et al. (93 )
	Mus musculus		HIF-1α expression	Lukashev et al. (94)
	Mus musculus		Accumulation of extracellular adenosine	Sitkovsky et al. (96)
	Human and Mus musculus		Treg recruitment	Facciabene et al. (97)
	Mus musculus	Treg differentiation	Th17 differentiation	Dang et al. (98)
	Human		Th17 survival	Kryczek et al. (100)
	Mus musculus	T cell-mediated cytotoxicity		MacDonald (105)
Low intratumor pH	Human and Mus musculus		Lymphocyte apoptosis	Lugini et al. (108), Calcinotto et al. (113)
	Mus musculus	CTL response in vivo	CTL activation in vitro	Droge et al. (109)
	Mus musculus	IL2-mediated T cell proliferation		Ratner (110)
	Mus musculus	CTL-mediated cytotoxicity		Redegeld et al. (111)
	Human	Proliferation and effector function of T cells		Fischer et al. (112)
	Human and Mus musculus	CTL proliferation, cytolitic activity and IL2, TNFα and IFNγ production		Calcinotto et al. (49)
Oxidative stress	Human and Mus musculus		Down-modulation of TCR CD3ζ chain	Rodriguez et al. (122), Rodriguez et al. (123)
	Mus musculus	Activation of JAK, STAT, ERK and AKT		Bingisser et al. (125), Mazzoni et al. (126)
	Mus musculus	Conformational flexibility of TCR and CD8 molecules		Nagaraj et al. (134)
	Human and Mus musculus	Intratumor infiltration of T cells		Molon et al. (135)
	Human		Release of cysteine and TRX by DCs	Angelini et al. (137)