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。
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
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.