Decreased expression in breast tumor cells causes NK cell activation and promotes tumor progression.

Objective: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B () has been detected in breast cancer but the function of remains unknown.

Methods: Western blot was used to analyze expression in breast cancer cells. The impact of on tumor cell migration and invasion was determined using Transwell assays, wound healing assays, and a mouse lung metastasis model. Subcutaneous tumor formation, a natural killer (NK) cell cytotoxicity assay, and flow cytometry evaluated NK cell activation. Immunofluorescence and quantitative real-time PCR detected NK cell activation markers. Kaplan-Meier analysis evaluated the effect of immune cell infiltration on prognosis. Single-sample gene set enrichment analysis determined NK cell activation scores. A support vector machine predicted the role of in NK cell activation.

Results: In this study we showed that inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that -mediated lactic acid clearance in breast cancer cells triggers NK cell activation within the tumor microenvironment. Our findings, which were confirmed in a murine model, demonstrated that in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that affects immune cell infiltration and function. Specifically, its expression has been linked to enhanced NK cell-mediated cytotoxicity and improved patient survival. Furthermore, we identified expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some cancers.

Conclusions: Our results suggest that is a promising target for activating the tumor immune microenvironment in breast cancer, where -associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of in regulating immune responses and its potential as a therapeutic target for breast cancer.