ABSTRACT
OBJECTIVE: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B (LDHB) has been detected in breast cancer but the function of LDHB remains unknown. METHODS: Western blot was used to analyze LDHB expression in breast cancer cells. The impact of LDHB 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 LDHB in NK cell activation. RESULTS: In this study we showed that LDHB inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that LDHB-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 LDHB in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that LDHB 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 LDHB expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some cancers. CONCLUSIONS: Our results suggest that LDHB is a promising target for activating the tumor immune microenvironment in breast cancer, where LDHB-associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of LDHB in regulating immune responses and its potential as a therapeutic target for breast cancer.
ABSTRACT
One-dimensional Zn-doped α-Fe2O3 nanowires have been controllably synthesized by using the pure pyrite as the source of Fe element through a two-step synthesis route, including the preparation of Fe source solution by a leaching process and the thermal conversion of the precursor solution into α-Fe2O3 nanowires by the hydrothermal and calcination process. The microstructure, morphology, and surface composition of the obtained products were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. It was found that the formation process of α-Fe2O3 is significantly influenced by the introduction of Zn2+. The gas sensing measurements indicated that the sensor based on 1% Zn-doped α-Fe2O3 nanowires showed excellent H2S sensing properties at the optimum operating temperature of 175 °C. Notably, the sensor showed a low H2S detection limit of 50 ppb with a sensor response of 1.5. Such high-performance sensing would be ascribed to the one-dimensional structure and high specific surface area of the prepared 1% Zn-doped α-Fe2O3 nanowires, which can not only provide a large number of surface active sites for the adsorption and reaction of the oxygen and H2S molecules, but also facilitate the diffusion of the gas molecules towards the entire sensing materials.
