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

Autor: Wieland A; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA. andreas.wieland@emory.edu.; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA. andreas.wieland@emory.edu., Patel MR; Department of Otolaryngology, Emory University School of Medicine, Atlanta, GA, USA.; Winship Cancer Institute of Emory University, Atlanta, GA, USA., Cardenas MA; Department of Urology, Emory University School of Medicine, Atlanta, GA, USA., Eberhardt CS; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA., Hudson WH; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA., Obeng RC; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.; Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA., Griffith CC; Winship Cancer Institute of Emory University, Atlanta, GA, USA.; Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA., Wang X; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA., Chen ZG; Winship Cancer Institute of Emory University, Atlanta, GA, USA.; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA., Kissick HT; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.; Winship Cancer Institute of Emory University, Atlanta, GA, USA.; Department of Urology, Emory University School of Medicine, Atlanta, GA, USA., Saba NF; Winship Cancer Institute of Emory University, Atlanta, GA, USA.; Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA., Ahmed R; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA. rahmed@emory.edu.; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA. rahmed@emory.edu.; Winship Cancer Institute of Emory University, Atlanta, GA, USA. rahmed@emory.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2021 Sep; Vol. 597 (7875), pp. 274-278. Date of Electronic Publication: 2020 Nov 18.
DOI: 10.1038/s41586-020-2931-3
Abstrakt: Tumours often contain B cells and plasma cells but the antigen specificity of these intratumoral B cells is not well understood 1-8 . 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.
(© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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