Tumor-derived lactate inhibit the efficacy of lenvatinib through regulating PD-L1 expression on neutrophil in hepatocellular carcinoma.
Haijing DengAnna KanNing LyuMeng HeXin HuangShuang QiaoShaolong LiWenhua LuQiankun XieHuiming ChenJinfa LaiQifeng ChenXiongying JiangShousheng LiuZhenfeng ZhangMing ZhaoPublished in: Journal for immunotherapy of cancer (2022)
PD-L1+ neutrophils decrease T cell cytotoxicity. Tumor-derived lactate induces PD-L1 expression on neutrophils via MCT1/NF-κB/COX-2 pathway. Thus, COX-2 inhibitor could reduce PD-L1+ neutrophil and restore T cell cytotoxicity. This may provide a potent addition to lenvatinib.