B cell deficiency promotes the initiation and progression of lung cancer
Han Wu, Chen Chen, Lixing Gu, Jia‐Peng Li, Yunqiang Yue, Mengqing Lyu, Yeting Cui, Xiaoyu Zhang, Yu Liu, Haichuan Zhu, Xing‐Hua Liao, Tongcun Zhang, Fan Sun, Weidong Hu
Abstract
Currently commercialized CAR-T cell therapies targeting CD19 and BCMA show great efficacy to cure B cell malignancies. However, intravenous infusion of these CAR-T cells severely destroys both transformed and normal B cells in most tissues and organs, in particular lung, leading to a critical question that what the impact of normal B cell depletion on pulmonary diseases and lung cancer is. Herein, we find that B cell frequency is remarkably reduced in both smoking carcinogen-treated lung tissues and lung tumors, which is associated with advanced cancer progression and worse patient survival. B cell depletion by anti-CD20 antibody significantly accelerates the initiation and progression of lung tumors, which is mediated by repressed tumor infiltration of T cells and macrophage elimination of tumor cells. These findings unveil the overall antitumor activity of B cells in lung cancer, providing novel insights into both mechanisms underlying lung cancer pathogenesis and clinical prevention post CAR-T cell therapy.