Table 3 Effects of lactate on immune cells in tumor microenvironment

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