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Scientific article
English

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

Published inNature, vol. 597, no. 7875, p. 274-278
Publication date2021-09-09
First online date2020-11-18
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.

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Keywords
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / genetics
  • Antibodies, Viral / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / virology
  • Cell Separation
  • Germinal Center / cytology
  • Germinal Center / immunology
  • Head and Neck Neoplasms / blood
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / virology
  • Humans
  • Immunity, Humoral
  • Immunoglobulin G / blood
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Papillomaviridae / immunology
  • Papillomavirus Infections / blood
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / virology
  • Plasma Cells / immunology
  • Plasma Cells / metabolism
  • RNA-Seq
  • Single-Cell Analysis
  • Somatic Hypermutation, Immunoglobulin / genetics
  • Somatic Hypermutation, Immunoglobulin / immunology
  • Transcriptome
  • Tumor Microenvironment / immunology
Affiliation Not a UNIGE publication
Funding
  • NCATS NIH HHS - [UL1 TR002378]
  • NIH HHS - [P51 OD011132]
Citation (ISO format)
WIELAND, Andreas et al. Defining HPV-specific B cell responses in patients with head and neck cancer. In: Nature, 2021, vol. 597, n° 7875, p. 274–278. doi: 10.1038/s41586-020-2931-3
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Article (Published version)
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Identifiers
ISSN of the journal0028-0836
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