MCT4/Lactate Promotes PD-L1 Glycosylation in Triple-Negative Breast Cancer Cells. (26th September 2022)

• Record Type: Journal Article
• Authors: Duan, Xianxian; Xie, Yu; Yu, Jing; Hu, Xiao; Liu, Zhanzhao; Li, Ning; Qin, Junfang; Lan, Lan; Yuan, Mengci; Pan, Zhanyu; Wang, Yue
• Other Names: Muthu Magesh Academic Editor.
• Is Part Of: Journal of oncology. Volume 2022(2022)
• Publication Date: 2022-09-26
• Subjects: Oncology -- Research -- Periodicals; Tumors -- Periodicals; Neoplasms; Oncology -- Research; Tumors; Periodicals; Periodicals; 616.994
• DOI: 10.1155/2022/3659714
• Languages: English
• ISSNs: 1687-8450

Abstract

Abstract : Triple-negative breast cancer (TNBC) has the highest percentage of lymphocytic infiltration among breast cancer subtypes, and TNBC patients may benefit from anti-PD-1/PD-L1 immunotherapy. However, some cases whether the immune checkpoint blockade (ICB) shows low targeting efficiency have occurred and effective synergistic targets need to be found, which inspired our exploration of the co-expression analysis of MCT4 (SLC16A3) and PD-L1 (CD274) and their potential regulatory mechanisms. After bioinformatic analysis of the relationship between MCT4 and PD-L1, we validated their positive co-expression relationship in triple-negative breast cancer through multiple immunohistochemical staining (mIHC), CRISPR/Cas9, and lentiviral transduction for MCT4 knockout (sgMCT4/231 KO) or overexpression (pEGFP-N1-MCT4/231). We examined the effect of lactate treatment on PD-L1 expression in triple-negative breast cancer cells by qRT-PCR and Western blot. Combined with our results, we found that MCT4 positively regulated PD-L1 expression through discharging lactate and stabilized PD-L1 through promoting its glycosylation by the classic WNT pathway in MDA-MB-231 cells. More importantly, the high co-expression of MCT4 and PD-L1 appears to predict more effective targets for treating TNBC, which would improve immune checkpoint therapy for TNBC.