Dahiana Amarillo1,2, Andreina Brugnini1, Natalia Trías1, Virginia Rodriguez Sande1, Siul Salisbury3, Mauricio Cuello2, Daniela Lens4. 1. Departamento Básico de Medicina, Hospital de Clínicas Dr. Manuel Quintela, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 2. Servicio de Oncología Médica, Hospital de Clínicas Dr. Manuel Quintela, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 3. Servicio de Cirugía Torácica, Hospital de Clínicas Dr. Manuel Quintela, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. 4. Departamento Básico de Medicina, Hospital de Clínicas Dr. Manuel Quintela, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. daniela.lens@gmail.com.
Abstract
INTRODUCTION: Regulatory T Cells (Tregs) play an important role in carcinogenesis and tumor immunoediting by preventing the development of effective antitumor immunity. Several reports showed that circulating Tregs are increased in patients with solid tumors, including lung cancer. Treg population could be categorized into "naive," "effector," and "memory" subtypes, bearing potential unique functions. However, the data regarding the prognostic impact of these Tregs subtypes is limited in lung cancer. The aim of this study was to investigate the frequency of different circulating Tregs subtypes in lung cancer and their correlation with clinical outcomes. METHODS: We analyzed the frequency of circulating CD4, CD8 and, Tregs lymphocytes in 66 patients with lung cancer and 32 healthy controls using flow cytometry. Circulating Tregs subtypes: naïve (CD3+ , CD4+ , CCR4+ , CD25+ and CD127low, CD45RO-), memory (CD3+ , CD4+ , CCR4+ , CD25+ and CD127low, CD45RO+) and the expression of the activation marker HLA-DR were correlated with overall survival. RESULTS: The percentage and the absolute number of total, memory and activated Tregs was significantly higher in lung cancer patients than healthy controls. Patients with a Tregs percentage higher than 5.4% and higher than 20% of HLA-DR + Tregs had worse overall survival than those with lower levels. CONCLUSIONS: Circulating Tregs and activated Tregs are a potential prognostic factor in patients with lung cancer treated with conventional therapy and could be considered a predictive biomarker in patients not eligible for immune blockade treatments. Additionally, it will be interesting to study these Tregs subsets for immune treatments in future clinical trials.
INTRODUCTION: Regulatory T Cells (Tregs) play an important role in carcinogenesis and tumor immunoediting by preventing the development of effective antitumor immunity. Several reports showed that circulating Tregs are increased in patients with solid tumors, including lung cancer. Treg population could be categorized into "naive," "effector," and "memory" subtypes, bearing potential unique functions. However, the data regarding the prognostic impact of these Tregs subtypes is limited in lung cancer. The aim of this study was to investigate the frequency of different circulating Tregs subtypes in lung cancer and their correlation with clinical outcomes. METHODS: We analyzed the frequency of circulating CD4, CD8 and, Tregs lymphocytes in 66 patients with lung cancer and 32 healthy controls using flow cytometry. Circulating Tregs subtypes: naïve (CD3+ , CD4+ , CCR4+ , CD25+ and CD127low, CD45RO-), memory (CD3+ , CD4+ , CCR4+ , CD25+ and CD127low, CD45RO+) and the expression of the activation marker HLA-DR were correlated with overall survival. RESULTS: The percentage and the absolute number of total, memory and activated Tregs was significantly higher in lung cancer patients than healthy controls. Patients with a Tregs percentage higher than 5.4% and higher than 20% of HLA-DR + Tregs had worse overall survival than those with lower levels. CONCLUSIONS: Circulating Tregs and activated Tregs are a potential prognostic factor in patients with lung cancer treated with conventional therapy and could be considered a predictive biomarker in patients not eligible for immune blockade treatments. Additionally, it will be interesting to study these Tregs subsets for immune treatments in future clinical trials.
Authors: Tao Lu; Xiaodong Yang; Yiwei Huang; Mengnan Zhao; Ming Li; Ke Ma; Jiacheng Yin; Cheng Zhan; Qun Wang Journal: Cancer Manag Res Date: 2019-01-21 Impact factor: 3.989