Atypical Memory and Regulatory B Cell Subsets in Tumor Draining Lymph Nodes of Head and Neck Squamous Cell Carcinoma Cor
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ORIGINAL PAPER
Atypical Memory and Regulatory B Cell Subsets in Tumor Draining Lymph Nodes of Head and Neck Squamous Cell Carcinoma Correlate with Good Prognostic Factors Marzieh Norouzian1 · Fereshteh Mehdipour2 · Sima Balouchi Anaraki1 · Mohammad Javad Ashraf3 · Bijan Khademi4 · Abbas Ghaderi1,2 Received: 8 June 2019 / Accepted: 30 October 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Research on the role of B cells in the development and modulation of antitumor immunity has increased in recent years; however, knowledge about B cell phenotype and function in tumor draining lymph nodes (TDLNs) is still incomplete. This study aimed to investigate changes in the phenotypic profile of B cells in TDLNs of head and neck squamous cell carcinoma (HNSCC) during disease progression. Mononuclear cells were isolated from TDLNs and stained with antibodies for CD19 and other B cell-related markers and analyzed by flow cytometry. C D19+ B cells comprised 38.6 ± 8.9% of lymphocytes in TDLNs of HNSCC. Comparison of metastatic and non-metastatic LNs disclosed no significant differences in the frequencies of B cell subsets including antigen-experienced, naïve, switched, unswitched, atypical memory, marginal zone-like B cells, and B cells with regulatory phenotypes. The percentage of atypical memory ( CD27–IgM–IgD–) B cells was significantly higher in patients with tongue SCC with no involved LNs (p = 0.033) and correlated inversely with the number of involved LNs. The frequency of CD24hiCD38hi B cells was significantly higher in non-metastatic LNs of patients with grade I compared to grade II (p = 0.016), and the percentage of CD5+ B cells decreased as tumors progressed from stage III to IV (p = 0.008). Our data show that in TDLNs of HNSCC, the frequency of B cells with atypical memory and regulatory phenotypes was significantly associated with good prognostic factors; however, their function remains to be investigated. Keywords B cells · Regulatory B cells · Tumor draining lymph nodes · HNSCC
Introduction
* Fereshteh Mehdipour [email protected] * Abbas Ghaderi [email protected] 1
Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
2
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, P.O. Box: 71345‑3119, Shiraz, Iran
3
Department of Oral Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
4
Department of Otolaryngology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
As the site of the first interaction between the tumor or tumor-related factors and the acquired immune system, tumor draining lymph nodes (TDLNs) have a unique position in the development of the immune response to tumors [1–3]. Under the influence of tumor products or tumor invasion, the immune profile of draining LNs apparently undergoes structural and cellular changes mostly in favor of further tumor progression [4–6]. Recent work has shown that the i
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