title: Reciprocal CD4+ T-cell balance of effector CD62Llow CD4+ and CD62LhighCD25+ CD4+ regulatory T cells in small cell lung cancer reflects disease stage.
abstract: OBJECTIVE
  Small cell lung cancer (SCLC) possesses high tendency to disseminate. However, SCLC patients with paraneoplastic syndrome mediated by immunity against onconeural antigens remain in limited-stage disease (LD) without distant metastases. Cumulative evidence regulates that a balance between immune and regulatory T (Treg) cells determines the magnitude of immune responses to not only self-antigens but also tumor-associated antigens. The purpose of this study was to elucidate the immunologic balance induced in SCLC patients.
  
  
  METHODS
  We analyzed T cells in the peripheral blood of 35 consecutive SCLC patients, 8 long-term survivors, and 19 healthy volunteers.
  
  
  RESULTS
  Purified CD4(+) T cells with down-regulated expression of CD62L (CD62L(low)) produced IFN-gamma, interleukin (IL)-4, and IL-17, thus considered to be immune effector T cells (Teff). Significantly more Teff cell numbers were detected in LD-SCLC patients than that of extended-stage SCLC (ED-SCLC). By contrast, induction of CD62L(high)CD25(+) CD4(+) Treg cells was significantly higher in ED-SCLC patients. Long-term survivors of SCLC maintained a high Teff to Treg cell ratio, whereas patients with recurrent disease exhibited a low Teff to Treg cell ratio. Teff cells in LD-SCLC patients included more IL-17-producing CD4(+) T cells (Th17). Moreover, dendritic cells derived from CD14(+) cells of LD-SCLC patients secreted more IL-23.
  
  
  CONCLUSIONS
  These results show that CD4(+) T-cell balance may be a biomarker that distinguishes ED-SCLC from LD-SCLC and predicts recurrence. This study also suggests the importance of inducing Teff cells, particularly Th17 cells, while eliminating Treg cells to control systemic dissemination of SCLC.
authors.affiliation: Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Course for Biological Functions and Medical Control, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Koyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kagamu
authors.forename: Satoru
authors.initials: S
authors.lastname: Miura
authors.forename: Toru
authors.initials: T
authors.lastname: Hiura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Miyabayashi
authors.forename: Ryo
authors.initials: R
authors.lastname: Itoh
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kuriyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Junta
authors.initials: J
authors.lastname: Tanaka
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yoshizawa
authors.forename: Koh
authors.initials: K
authors.lastname: Nakata
authors.forename: Fumitake
authors.initials: F
authors.lastname: Gejyo
mesh_terms: D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000032:analysis*; D005260:Female; D006801:Humans; D019041:L-Selectin / Q000032:analysis*; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D019041:L-Selectin