title: Prognostic value of circulating regulatory T cell subsets in untreated non-small cell lung cancer patients.
abstract: The role of the different circulating regulatory T-cells (Treg) subsets, as well as their correlation with clinical outcome of non-small cell lung cancer (NSCLC) patients is poorly understood. Peripheral blood from 156 stage III/IV chemotherapy-naive NSCLC patients and 31 healthy donors (HD) was analyzed with flow cytometry for the presence and functionality of CD4+Treg subsets (naive, effector and terminal effector). Their frequencies were correlated with the clinical outcome. All CD4+Treg subsets exhibited highly suppressive activity by TGF-β and IL-10 production. The percentages of naive Treg were found elevated in NSCLC patients compared to HD and were associated with poor clinical outcome, whereas the percentage of terminal effector Treg was lower compared to HD and higher levels were correlated with improved clinical response. At baseline, normal levels of naive and effector Treg were associated with longer overall survival (OS) compared to high levels, while the high frequency of the terminal effector Treg was correlated with longer Progression-Free Survival and OS. It is demonstrated, for first time, that particular CD4+Treg subtypes are elevated in NSCLC patients and their levels are associated to the clinical outcome. The blocking of their migration to the tumor site may be an effective therapeutic strategy.
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Voutes, GR-71110, Heraklion, Crete, Greece.|Department of Medical Oncology, University Hospital of Heraklion, Voutes, GR-71110, Heraklion, Crete, Greece.|Hellenic Society of Immuno-Oncology, 55 Lombardou str., 11474, Athens, Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Kotsakis
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Voutes, GR-71110, Heraklion, Crete, Greece.|Department of Medical Oncology, University Hospital of Heraklion, Voutes, GR-71110, Heraklion, Crete, Greece.|Hellenic Society of Immuno-Oncology, 55 Lombardou str., 11474, Athens, Greece.
authors.forename: Filippos
authors.initials: F
authors.lastname: Koinis
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Voutes, GR-71110, Heraklion, Crete, Greece.|Hellenic Society of Immuno-Oncology, 55 Lombardou str., 11474, Athens, Greece.
authors.forename: Afroditi
authors.initials: A
authors.lastname: Katsarou
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Voutes, GR-71110, Heraklion, Crete, Greece.|Hellenic Society of Immuno-Oncology, 55 Lombardou str., 11474, Athens, Greece.
authors.forename: Marianthi
authors.initials: M
authors.lastname: Gioulbasani
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Voutes, GR-71110, Heraklion, Crete, Greece.|Hellenic Society of Immuno-Oncology, 55 Lombardou str., 11474, Athens, Greece.
authors.forename: Despoina
authors.initials: D
authors.lastname: Aggouraki
authors.affiliation: Hellenic Society of Immuno-Oncology, 55 Lombardou str., 11474, Athens, Greece.|Department of Medical Oncology, 251 Air Force Hospital, Leof. P. Kanellopoulou, 115 25, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kentepozidis
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Voutes, GR-71110, Heraklion, Crete, Greece.|Department of Medical Oncology, University Hospital of Heraklion, Voutes, GR-71110, Heraklion, Crete, Greece.|Hellenic Society of Immuno-Oncology, 55 Lombardou str., 11474, Athens, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
authors.affiliation: Laboratory of Translational Oncology, School of Medicine, University of Crete, Voutes, GR-71110, Heraklion, Crete, Greece.|Hellenic Society of Immuno-Oncology, 55 Lombardou str., 11474, Athens, Greece.
authors.forename: Eleni-Kyriaki
authors.initials: EK
authors.lastname: Vetsika
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015704:CD4 Antigens / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015704:CD4 Antigens; D016212:Transforming Growth Factor beta; D016753:Interleukin-10