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研究揭示头颈癌患者的HPV特异性B细胞反应
2020-11-20 14:39

美国埃默里大学医学院Rafi Ahmed、Andreas Wieland等研究人员合作定义了头颈癌患者的HPV特异性B细胞反应。该项研究成果于2020年11月18日在线发表在《自然》杂志上。

研究人员发现,人类乳头瘤病毒(HPV)特异的B细胞反应可在具有HPV阳性头颈癌患者的样本中检测到,并原位产生HPV特异性IgG抗体。HPV特异性抗体分泌细胞(ASC)存在于肿瘤微环境中,最小的旁观者招募了流感特异性细胞,这表明存在局部和抗原特异性ASC反应。HPV特异的ASC反应与血浆IgG的效价相关,并针对HPV蛋白E2、E6和E7,其中对E2的反应最为明显。使用肿瘤内B细胞和浆细胞,研究人员产生了几种HPV特异性人类单克隆抗体,并表现出高度的体细胞超突变,与慢性抗原暴露一致。
 
单细胞RNA测序分析可检测到肿瘤微环境中活化的B细胞、生发中心B细胞和ASC。与肿瘤实质相比,B细胞和ASC优先定位在肿瘤基质中,并具有活化B细胞形成的簇,这表明正在进行的生发中心反应。
 
总的来说,研究人员发现在肿瘤微环境中可以发现抗原特异性的活化和生发中心B细胞以及浆细胞。这些发现为人类癌症中的体液免疫反应提供了更好的理解,并提示可以利用肿瘤浸润性B细胞开发治疗剂。
 
据悉,肿瘤通常包含B细胞和浆细胞,但这些肿瘤内B细胞的抗原特异性尚不清楚。
 
附:英文原文

Title: Defining HPV-specific B cell responses in patients with head and neck cancer

Author: Andreas Wieland, Mihir R. Patel, Maria A. Cardenas, Christiane S. Eberhardt, William H. Hudson, Rebecca C. Obeng, Christopher C. Griffith, Xu Wang, Zhuo G. Chen, Haydn T. Kissick, Nabil F. Saba, Rafi Ahmed

Issue&Volume: 2020-11-18

Abstract: Tumours often contain B cells and plasma cells but the antigen specificity of these intratumoral B cells is not well understood1–8. Here we show that human papillomavirus (HPV)-specific B cell responses are detectable in samples from patients with HPV-positive head and neck cancers, with active production of HPV-specific IgG antibodies in situ. HPV-specific antibody secreting cells (ASCs) were present in the tumour microenvironment, with minimal bystander recruitment of influenza-specific cells, suggesting a localized and antigen-specific ASC response. HPV-specific ASC responses correlated with titres of plasma IgG and were directed against the HPV proteins E2, E6 and E7, with the most dominant response against E2. Using intratumoral B cells and plasma cells, we generated several HPV-specific human monoclonal antibodies, which exhibited a high degree of somatic hypermutation, consistent with chronic antigen exposure. Single-cell RNA sequencing analyses detected activated B cells, germinal centre B cells and ASCs within the tumour microenvironment. Compared with the tumour parenchyma, B cells and ASCs were preferentially localized in the tumour stroma, with well-formed clusters of activated B cells indicating ongoing germinal centre reactions. Overall, we show that antigen-specific activated and germinal centre B cells as well as plasma cells can be found in the tumour microenvironment. Our findings provide a better understanding of humoral immune responses in human cancer and suggest that tumour-infiltrating B cells could be harnessed for the development of therapeutic agents. Detailed analyses of B cells in the tumour microenvironment of human papilloma virus (HPV)-linked head and neck cancers reveal strong humoral immune responses to HPV antigens and the secretion of HPV-specific antibodies in situ.

DOI: 10.1038/s41586-020-2931-3

Source: https://www.nature.com/articles/s41586-020-2931-3

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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