Poster #094
MCT4 Inhibitor Reverses Lactate-Induced PD-L1 Upregulation in TNBC Cells
Mentors: Ke Wu, MD, PhD; PI: Piwen Wang, PhD
Triple-negative breast cancer (TNBC) is an aggressive, hard-to-treat breast cancer subtype lacking hormone and HER2 receptors. TNBC cells like MDA-MB-231 exhibit elevated glycolysis, producing excess lactate, which is exported via monocarboxylate transporter 4 (MCT4), acidifying the tumor microenvironment and promoting immune evasion. SLC16A3 (MCT4) and CD274 (PD-L1) are positively correlated in both normal breast tissue and TNBC, suggesting a metabolic-immune link in tumor progression. Systematic studies show MCT4-driven lactate efflux activates WNT signaling, increasing PD-L1 expression and stability. In this study, MDA-MB-231 cells were treated with lactate, with or without a novel MCT4 inhibitor. We measured lactate levels, extracellular pH, PD-L1 mRNA via qRT-PCR, total PD-L1 protein by Western blot, and surface PD-L1 through flow cytometry. The inhibitor reduced lactate export, restored pH, and suppressed PD-L1 expression at multiple levels. These results highlight MCT4 as a key regulator of immune evasion and a promising therapeutic target in TNBC.