Introduction: Recently, we have shown that human regulatory B cells (Breg) and regulatory T cells (Treg) are the main producers of exogenous immune-suppressive adenosine (ADO) with the ectonucleotidases, CD39 and CD73, being the functional enzymes. Immune suppression in the tumor environment may cause increased tumor growth and metastasis. But the role of intracellular components of Breg and in response to ADO are not completely understood.
Methods: Peripheral blood mononuclear cells (PBMC) and tumor infiltrating lymphocytes (TIL) were isolated from patients with head and neck cancer (n = 20). Phenotypes, intracellular expression of phosphor-proteins of the B cell-receptor (BCR)-mediated signaling pathway and ADO production were determined by multicolor flow cytometry and luminescence. The influence of exogenous ADO on intracellular signaling pathways was determined by flow cytometry, western blot and PCR on healthy volunteers.
Results: In comparison to healthy donors, the frequency of Treg is increased while the frequency of Breg remains stable in the peripheral blood of cancer patients. For the Treg this effect is pronounced in the tumor microenvironment, while the B cells showed new phenotypic characteristics. The phosphorylation of the proteins of the intracellular BCR-pathway in healthy B cells are inhibited by treatment with ADO. In contrast, after BCR-specific stimulation, the secretion of inflammatory cytokines by B cells is increased in the presence of ADO.
Conclusion: Adenosine producing immune cells contribute to immune suppression in the tumor microenvironment and may promote tumor growth. Intracellular key regulators of ADO-production in Breg may serve as a therapeutic target in cancer patients.
Citation Format: Sandra S. Jäkle, Cornelia Brunner, Thomas K. Hoffmann, Patrick J. Schuler. Characterization of adenosine producing B cells in patients with head and neck cancer as well as of the influence of adenosine on B cell function [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A105.
- ©2016 American Association for Cancer Research.