Unique characteristics of autoantibodies targeting MET in patients with breast and lung cancer.

IF 6.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Michal Navon, Noam Ben-Shalom, Maya Dadiani, Michael Mor, Ron Yefet, Michal Bakalenik-Gavry, Dana Chat, Nora Balint-Lahat, Iris Barshack, Ilan Tsarfaty, Einav Nili Gal-Yam, Natalia T Freund
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引用次数: 0

Abstract

The presence of B cells in tumors is correlated with favorable prognosis and efficient response to immunotherapy. While tumor-reactive antibodies have been detected in several cancer types, identifying antibodies that specifically target tumor-associated antigens remains a challenge. Here, we investigated the antibodies spontaneously elicited during breast and lung cancer that bind the cancer-associated antigen MET. We screened patients with lung (n = 25) and breast (n = 75) cancer and found that 13% had antibodies binding to both the recombinant ectodomain of MET, and the ligand binding part of MET, SEMA. MET binding in the breast cancer cohort was significantly correlated with hormone receptor-positive status. We further conducted immunoglobulin sequencing of peripheral MET-enriched B cells from 6 MET-reactive patients. The MET-enriched B cell repertoire was found to be polyclonal and prone to non-IgG1 subclass. Nine monoclonal antibodies were cloned and analyzed, and these exhibited MET binding, low thermostability, and high polyreactivity. Among these, antibodies 87B156 and 69B287 effectively bound to tumor cells and inhibited MET-expressing breast cancer cell lines. Overall, our data demonstrate that some patients with breast and lung cancer develop polyreactive antibodies that cross-react with MET. These autoantibodies have a potential contribution to immune responses against tumors.

针对乳腺癌和肺癌患者MET的自身抗体的独特特征。
B细胞在肿瘤中的存在与良好的预后和对免疫治疗的有效反应有关。虽然肿瘤反应性抗体已经在几种癌症类型中被检测到,但识别特异性靶向肿瘤相关抗原的抗体仍然是一个挑战。在这里,我们研究了在乳腺癌和肺癌期间自发引发的结合癌症相关抗原MET的抗体。我们筛选了肺癌(n = 25)和乳腺癌(n = 75)患者,发现13%的患者具有结合MET重组外结构域和MET配体结合部分SEMA的抗体。乳腺癌队列中的MET结合与激素受体阳性状态显著相关。我们进一步对6例met反应患者外周血富集met的B细胞进行免疫球蛋白测序。发现met富集的B细胞库是多克隆的,并且倾向于非igg1亚类。我们克隆并分析了9个单克隆抗体,这些单克隆抗体具有MET结合、低热稳定性和高多反应性。其中,87B156和69B287抗体能有效结合肿瘤细胞,抑制表达met的乳腺癌细胞系。总的来说,我们的数据表明,一些乳腺癌和肺癌患者会产生与MET交叉反应的多反应性抗体。这些自身抗体对肿瘤的免疫反应有潜在的贡献。
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来源期刊
JCI insight
JCI insight Medicine-General Medicine
CiteScore
13.70
自引率
1.20%
发文量
543
审稿时长
6 weeks
期刊介绍: JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
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