Reciprocal CD4+ T-cell balance of effector CD62Llow CD4+ and CD62LhighCD25+ CD4+ regulatory T cells in small cell lung cancer reflects disease stage.
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.
Koyama
Kenichi
K
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.
Kagamu
Hiroshi
H
Miura
Satoru
S
Hiura
Toru
T
Miyabayashi
Takahiro
T
Itoh
Ryo
R
Kuriyama
Hideyuki
H
Tanaka
Hiroshi
H
Tanaka
Junta
J
Yoshizawa
Hirohisa
H
Nakata
Koh
K
Gejyo
Fumitake
F
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*
D015704:CD4 Antigens; D019041:L-Selectin