The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cells

The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cells

Abstract Tumor acidosis, a common phenomenon in solid cancers such as breast cancer, is caused by the abnormal metabolism of cancer cells. The low pH affects cells surrounding the cancer, and tumor acidosis has been shown to inhibit the activity of immune cells. Despite many previous studies, the im...

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Bibliographic Details
Published in:BMC cancer 2022-08, Vol.22 (1), p.1-852, Article 852
Main Authors: Kwon, Yong-Jin, Seo, Eun-Bi, Jeong, Ae Jin, Lee, Song-Hee, Noh, Kum Hee, Lee, Sangsik, Cho, Chung-Hyun, Lee, Chang-Han, Shin, Hyun Mu, Kim, Hang-Rae, Moon, Hyeong-Gon, Ye, Sang-Kyu
Format: Article
Language:eng
Subjects:
Acidosis
Acids
Antibodies
Apoptosis
Breast cancer
Cancer therapies
Cell culture
Extracellular acidosis
Gene set enrichment analysis
Genes
Immune checkpoint
Immunosurveillance
Interleukin 6
Laboratories
MDA-MB-231 cells
Membranes
Metastasis
PD-L1
PD-L1 protein
pH effects
Proteins
Sodium
Software
STAT3
Stat3 protein
Statistical analysis
Tumor microenvironment
Tyrosine
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Summary:Abstract Tumor acidosis, a common phenomenon in solid cancers such as breast cancer, is caused by the abnormal metabolism of cancer cells. The low pH affects cells surrounding the cancer, and tumor acidosis has been shown to inhibit the activity of immune cells. Despite many previous studies, the immune surveillance mechanisms are not fully understood. We found that the expression of PD-L1 was significantly increased under conditions of extracellular acidosis in MDA-MB-231 cells. We also confirmed that the increased expression of PD-L1 mediated by extracellular acidosis was decreased when the pH was raised to the normal range. Gene set enrichment analysis (GSEA) of public breast cancer patient databases showed that PD-L1 expression was also highly correlated with IL-6/JAK/STAT3 signaling. Surprisingly, the expression of both phospho-tyrosine STAT3 and PD-L1 was significantly increased under conditions of extracellular acidosis, and inhibition of STAT3 did not increase the expression of PD-L1 even under acidic conditions in MDA-MB-231 cells. Based on these results, we suggest that the expression of PD-L1 is increased by tumor acidosis via activation of STAT3 in MDA-MB-231 cells.
ISSN:1471-2407
1471-2407