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

Nature
Andreas WielandRafi 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 ce...Continue Reading

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Citations

Dec 20, 2020·Nature Reviews. Cancer·Sarah Seton-Rogers
Jan 13, 2021·Nature Reviews. Immunology·Sarah Seton-Rogers
May 25, 2021·Molecular Therapy Oncolytics·Guangshun SunYangbai Sun
Jun 1, 2021·Frontiers in Immunology·Marta Trüb, Alfred Zippelius
Sep 3, 2021·Nature·Christiane S EberhardtRafi Ahmed
Sep 3, 2021·International Journal of Radiation Oncology, Biology, Physics·Ida Franiak-PietrygaAndrew B Sharabi
Nov 19, 2021·JAMA Otolaryngology-- Head & Neck Surgery·Nicole C Schmitt

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