Table 3.

Effects of lactate on immune cells in tumor microenvironment

Cell type	Mechanism	Effect
macrophages	Activation of the ERK-STAT3 pathway	M2 polarization (↑IL-6, ↑VEGF, ↑ARG1, ↑CCL5)
	Activation of GPR132 and Notch
	HIF1α stablization
	Histone lactylation
T cell	Acidic pH environment	↓Effector function
	Activation PD-L1/PD-1 pathway	↓Proliferation
	Inhibition of p38 and JNK–JUN	↑PD-1
	Inhibition of lactate efflux	↑Apoptosis
	Reduced NAD availability	↓Cytokine production
Dendritic cell	Acidic pH environment	↓Differentiation
	Reduced CD1a and increased CD14 expression	↓IL-12
	Activation of GPR81 and import via SLC16A	↓IL-6
		↓TNF
		↑Kynurenine
Treg cell	FOXP3-mediated repression of MYC and modulation of LDH	↑Proliferation
	Sustained fatty acid synthesis through ACC	↑Differentiation
		↑TGFβ
		↑IL-10
NK cell	Inhibition of NFAT and NKp46	↓Cytolytic function
	Inhibition of mTOR signaling	↓IFNγ
	Acidic pH environment	↑Apoptosis
	HDAC inhibition