The influence of chemotherapy on adenosine-producing B cells in patients with head and neck squamous cell carcinoma

Oncotarget
Andreas ZiebartPatrick J Schuler

Abstract

Head and neck squamous cell carcinoma (HNSCC) strongly suppresses the immune system, resulting in increased metastasis and recurrent disease. Chemotherapy is part of the multimodal treatment but may further immunosuppression. Recently, we demonstrated that regulatory B cells (Breg), defined as CD19+CD39+CD73+ B cells, play a significant role in the production of immunosuppressive, extracellular adenosine (ADO). Here, we tested the influence of chemotherapy on Breg function. In HNSCC patients, Breg were diminished in absolute number and frequency after chemotherapy (paired samples). Chemotherapeutic drugs had variable effects; while platinum-based chemotherapy decreased the expression of CD39, methotrexate led to a functional increase in CD39 expression and increased production of immunosuppressive ADO. These findings were confirmed in a second patient cohort. Surface expression of CD39 correlated strongly with the production of ADO as measured by mass spectrometry. Platinum-based anti-tumor-therapy reduces the number of adenosine-producing B cells and, consequently, potential immunosuppression within the tumor environment. Breg function in terms of ADO production and their potential capacity to suppress CD4+ T cells are promote...Continue Reading

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Citations

Mar 1, 2019·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·S S JeskeJohannes Doescher
Mar 4, 2018·HNO·P J SchulerT K Hoffmann
Mar 9, 2020·Cancer Immunology, Immunotherapy : CII·Sandra S JeskePatrick J Schuler
Dec 6, 2020·Journal of Clinical Medicine·Avital VorontsovaYuval Shaked

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Methods Mentioned

BETA
flow cytometry
blood draws
Assay

Clinical Trials Mentioned

NCT02503774
NCT02403193

Software Mentioned

Kaluza ® flow cytometry
GraphPad Prism

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