Simultaneous glutamine metabolism and PD-L1 inhibition to enhance suppression of triple-negative breast cancer

作者：Yuxia Tang, Siqi Wang, Siqi Wang, Yang Li, Chen Yuan, Jie Zhang, Yongzhi Hu, Yongzhi Hu, Haibin Shi, Shouju Wang, Shouju Wang · 发表于：Journal of Nanobiotechnology · 年份：2022 · DOI：10.1186/s12951-022-01424-7 · 被引用次数：46 · 研究领域：Cancer Research and Treatments、Cancer Immunotherapy and Biomarkers、Cancer, Hypoxia, and Metabolism

Abstract Blockade of programmed cell death 1 ligand (PD-L1) has been used to treat triple-negative breast cancer (TNBC), and various strategies are under investigation to improve the treatment response rate. Inhibition of glutamine metabolism can reduce the massive consumption of glutamine by tumor cells and meet the demand for glutamine by lymphocytes in tumors, thereby improving the anti-tumor effect on the PD-L1 blockade therapy. Here, molybdenum disulfide (MoS 2 ) was employed to simultaneously deliver anti-PDL1 antibody (aPDL1) and V9302 to boost the anti-tumor immune response in TNBC cells. The characterization results show that MoS 2 has a dispersed lamellar structure with a size of about 181 nm and a size of 232 nm after poly ( l -lysine) (PLL) modification, with high stability and biocompatibility. The loading capacity of aPDL1 and V9302 are 3.84% and 24.76%, respectively. V9302 loaded MoS 2 (MoS 2 -V9302) can effectively kill 4T1 cells and significantly reduce glutamine uptake of tumor cells. It slightly increases CD8 + cells in the tumor and promotes CD8 + cells from the tumor edge into the tumor core. In vivo studies demonstrate that the combination of aPDL1 and V9302 (MoS 2 -aPDL1-V9302) can strongly inhibit the growth of TNBC 4T1 tumors. Interestingly, after the treatment of MoS 2 -aPDL1-V9302, glutamine levels in tumor interstitial fluid increased. Subsequently, subtypes of cytotoxic T cells (CD8 + ) in the tumors were analyzed according to two markers of T cel...