Non-progressing cancer patients have persistent B cell responses expressing shared antibody paratopes that target public tumor antigens
Non-progressing cancer patients have persistent B cell responses expressing shared antibody paratopes that target public tumor antigens
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DOI：
10.1016/j.clim.2017.10.002
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发表时间：
2018-02-01
影响因子：
8.6
通讯作者：
Robinson, William H.
中科院分区：
文献类型：
--
作者：
DeFalco, Jeff;Harbell, Michael;Robinson, William H.
关于B细胞和它们的抗体是否有助于有效的抗癌免疫应答存在重大争论。在这里，我们发现，转移性但非进展性黑色素瘤，肺腺癌，或肾细胞癌患者表现出增加的血浆母细胞水平。我们使用细胞条形码技术对其浆母细胞抗体库进行测序，揭示了亲和力成熟的B细胞的克隆家族，这些细胞随着时间的推移表现出渐进的类别转换和持久性。抗CTLA4和其他治疗与体细胞超突变和克隆家族大小的进一步增加相关。来自克隆家族的重组抗体结合非自体肿瘤组织和细胞系，并且具有患者之间共享的免疫球蛋白互补位序列基序的家族表现出增加的结合率。我们鉴定了引起小鼠异源同基因肿瘤消退和持久免疫的抗体。我们的研究结果证明了针对公共肿瘤抗原的会聚功能性抗肿瘤抗体应答，并提供了鉴定具有诊断或治疗效用的抗体的方法。(C)2017作者爱思唯尔公司出版
There is significant debate regarding whether B cells and their antibodies contribute to effective anti-cancer immune responses. Here we show that patients with metastatic but non-progressing melanoma, lung adenocarcinoma, or renal cell carcinoma exhibited increased levels of blood plasmablasts. We used a cell-barcoding technology to sequence their plasmablast antibody repertoires, revealing clonal families of affinity matured B cells that exhibit progressive class switching and persistence over time. Anti-CTLA4 and other treatments were associated with further increases in somatic hypermutation and clonal family size. Recombinant antibodies from clonal families bound non-autologous tumor tissue and cell lines, and families possessing immunoglobulin paratope sequence motifs shared across patients exhibited increased rates of binding. We identified antibodies that caused regression of, and durable immunity toward, heterologous syngeneic tumors in mice. Our findings demonstrate convergent functional anti-tumor antibody responses targeting public tumor antigens, and provide an approach to identify antibodies with diagnostic or therapeutic utility. (C) 2017 The Authors. Published by Elsevier Inc.