Lactic acid regulates the activation and function of DC in tumors
LI Chengyin
ZHAO Jingling
WANG Qiyuan
ZHU Jing
QIN Danmei
Abstract：This study was performed to investigate the effect of lactic acid on the activation and function of dendritic cells in tumor microenvironment.Bone marrow cells were isolated from C57BL/6 mice and induced to differentiate into DCs,followed by lipopolysaccharide stimulation to promote its activation.Then the activated DCs were treated with tumor cell culture supernatant or lactic acid,the activation of DCs were detected by flow cytometry,ELISA,T cell proliferation assay,Western blot and other methods.In addition,the activation of signaling pathways in DCs were analyzed.Data showed that more lactic acid was released by tumor cells in the hypoxic state;lactic acid could inhibit the expression of CD80,CD86 and MHC Ⅱ,and downregulate the expression of TNF-α and IL-12 to suppress the ability of DC to promote T cell activation and proliferation.Furthermore,lactic acid affects the activation of DC by inhibiting the activation of NF-κB and p38MAPK signaling pathways.Taken together,a large amount of lactic acid are released by hypoxic tumor cells,which inhibit the activation of DC cells and suppress the anti-tumor immune responses.
Keywords：Dendritic cellsTumor microenvironmentHypoxiaLactic acid
Publication Date：2017-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 405-409 )