肿瘤细胞治疗研究
英文原题：B cell deficiency promotes the initiation and progression of lung cancer.
目前商业化的靶向 CD19 和 BCMA 的 CAR-T 细胞疗法在治疗 B 细胞恶性肿瘤方面显示出巨大疗效。
目前针对CD19和BCMA的已商业化CAR-T细胞疗法在治愈B细胞恶性肿瘤方面显示出巨大疗效。然而，静脉输注这些CAR-T细胞会严重破坏大多数组织和器官中的转化B细胞和正常B细胞，尤其是肺部，这引出了一个关键问题：正常B细胞耗竭对肺部疾病和肺癌的影响是什么。在此，我们发现，在吸烟致癌物处理的肺组织和肺肿瘤中，B细胞频率显著降低，这与癌症进展期和患者生存期较差相关。通过抗CD20抗体耗竭B细胞显著加速了肺肿瘤的发生和进展，这是由T细胞肿瘤浸润受抑和巨噬细胞对肿瘤细胞的清除所介导的。这些发现揭示了B细胞在肺癌中的整体抗肿瘤活性，为肺癌发病机制以及CAR-T细胞治疗后临床预防提供了新的见解。
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.
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