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RNA-sequencing analysis of tumor-infiltrating B cells

ABSTRACT: Tumour-infiltrating lymphocytes are a major predictor for overall survival and response to immunotherapy for several malignancies. However, while tumour-infiltrating CD8 T cells have been extensively studied, little is known about the role of the humoral immune system within the tumour microenvironment (TME). Here we show that plasma cells are present in the TME and actively secrete human papillomavirus (HPV)-specific IgG antibodies in HPV-positive head and neck squamous cell carcinoma patients. Compared to circulating memory B cells, plasma cells in the TME were enriched for HPV-reactivity with little bystander recruitment of influenza-specific cells. HPV-specific plasma cells in the TME correlated with the antibody titres in peripheral blood and produced antibodies with a high degree of somatic hypermutation directed against HPV E2, E6 and E7 antigens. A striking proportion of HPV-specific antibodies produced in situ were directed against E2, which might thus be a promising target for immunotherapies in HPV-associated cancers. Overall, we show that antigen-specific activated and germinal centre B cells as well as plasma cells can be found in the TME, with plasma cells producing antibodies specific for tumour-associated antigens in situ. These 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 novel therapeutic agents.

ORGANISM(S): Homo sapiens

PROVIDER: GSE149327 | GEO | 2020/07/20

REPOSITORIES: GEO

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