研究揭示頭頸癌患者的HPV特異性B細胞反應
作者：
小柯機器人發布時間：2020/11/20 14:39:54
美國埃默裡大學醫學院Rafi Ahmed、Andreas Wieland等研究人員合作定義了頭頸癌患者的HPV特異性B細胞反應。該項研究成果於2020年11月18日在線發表在《自然》雜誌上。
研究人員發現，人類乳頭瘤病毒（HPV）特異的B細胞反應可在具有HPV陽性頭頸癌患者的樣本中檢測到，並原位產生HPV特異性IgG抗體。HPV特異性抗體分泌細胞（ASC）存在於腫瘤微環境中，最小的旁觀者招募了流感特異性細胞，這表明存在局部和抗原特異性ASC反應。HPV特異的ASC反應與血漿IgG的效價相關，並針對HPV蛋白E2、E6和E7，其中對E2的反應最為明顯。使用腫瘤內B細胞和漿細胞，研究人員產生了幾種HPV特異性人類單克隆抗體，並表現出高度的體細胞超突變，與慢性抗原暴露一致。
單細胞RNA測序分析可檢測到腫瘤微環境中活化的B細胞、生發中心B細胞和ASC。與腫瘤實質相比，B細胞和ASC優先定位在腫瘤基質中，並具有活化B細胞形成的簇，這表明正在進行的生發中心反應。
總的來說，研究人員發現在腫瘤微環境中可以發現抗原特異性的活化和生發中心B細胞以及漿細胞。這些發現為人類癌症中的體液免疫反應提供了更好的理解，並提示可以利用腫瘤浸潤性B細胞開發治療劑。
據悉，腫瘤通常包含B細胞和漿細胞，但這些腫瘤內B細胞的抗原特異性尚不清楚。
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