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10780432ccr130900-sup-fig_s1_legends.pdf (34.42 kB)

Legend to Figure S1 from Effects of Adjuvant Chemoradiotherapy on the Frequency and Function of Regulatory T Cells in Patients with Head and Neck Cancer

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posted on 2023-03-31, 17:27 authored by Patrick J. Schuler, Malgorzata Harasymczuk, Bastian Schilling, Zenichiro Saze, Laura Strauss, Stephan Lang, Jonas T. Johnson, Theresa L. Whiteside

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ARTICLE ABSTRACT

Purpose: Regulatory T cells (Treg) accumulate in tumor tissues and the peripheral blood of cancer patients and may persist after therapies. This cross-sectional study examines effects of adjuvant chemoradiotherapy (CRT) on Treg numbers and function in head and neck squamous cell carcinoma (HNSCC) patients.Experimental Design: The frequency and absolute numbers of CD4+, ATP-hydrolyzing CD4+CD39+ and CD8+ T cells, and expression levels of CD39, CD25, TGF-β–associated LAP and GARP on Treg were measured by flow cytometry in 40 healthy donors (NC) and 71 HNSCC patients [29 untreated with active disease (AD); 22 treated with surgery; 20 treated with CRT]. All treated subjects had no evident disease (NED) at the time of phlebotomy. In an additional cohort of 40 subjects with AD (n = 15), NED (n = 10), and NC (n = 15), in vitro sensitivity of CD4+ T-cell subsets to cisplatin and activation-induced cell death (AICD) was tested in Annexin V–binding assays.Results: CRT decreased the frequency of circulating CD4+ T cells (P < 0.002) but increased that of CD4+CD39+ Treg (P ≤ 0.001) compared with untreated or surgery-only patients. Treg frequency remained elevated for >3 years. CRT increased surface expression of LAP, GARP, and CD39 on Treg. In vitro Treg were resistant to AICD or cisplatin but conventional CD4+ T cells (Tconv) were not. CRT-induced Treg from AD or NC subjects upregulated prosurvival proteins whereas Tconv upregulated proapoptotic Bax.Conclusions: Highly suppressive, cisplatin-resistant Treg increase in frequency and persist after CRT and could be responsible for suppression of antitumor immune responses and recurrence in HNSCC. Clin Cancer Res; 19(23); 6585–96. ©2013 AACR.