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Defining HPV-Specific B Cell Responses in Patients with Head and Neck Cancer

Authors: 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

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

Issue: Nature. 2020 Nov 18


Tumours often contain B cells and plasma cells but the antigen specificity of these intratumoral B cells is not well understood1,2,3,4,5,6,7,8. 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.