Effects of adjuvant chemoradiotherapy on the frequency and function of regulatory T cells in patients with head and neck cancer
Menée sur deux cohortes de 71 et 40 patients atteints d'un carcinome épidermoïde de la tête et du cou, cette étude transversale analyse les effets d'une chimioradiothérapie adjuvante sur le nombre de lymphocytes T régulateurs s'accumulant au niveau du tissu tumoral et met en évidence leur rôle dans l'apparition d'une récidive
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 chemo-radiotherapy (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 to 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 up-regulated pro-survival proteins, while Tconv up-regulated pro-apoptotic Bax. Conclusions : Highly suppressive, cisplatin-resistant Treg increase in frequency and persist after CRT and could be responsible for suppression of anti-tumor immune responses and recurrence in HNSCC.