| Project/Area Number |
18590841
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Niigata University |
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Principal Investigator |
KAGAMU Hiroshi Niigata University, Institute of Medicine and Dentistry, Assistant Professor (30418686)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATA Koh Niigata University, Medical and Dental Hospital, Professor (80207802)
YOSHIZAWA Hirohisa Niigata University, Medical and Dental Hospital, Associate Professor (50282984)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | small cell lung cancer / regulatory T cell / antitumor effector CD4 T cell / 抗腫瘍エフェクターCD4T細胞 |
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| Research Abstract |
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 cells (Treg) determines the magnitude of immune responses to not only self-antigens but also tumor-associated antigens. Here, we analyzed T cells in the peripheral blood of 35 consecutive SCLC patients, 8 long-term survivors, and 19 healthy volunteers to assess the balance of CD4^+ T cells. Purified CD4^+ T cells with down-regulated expression of CD62L (CD62L^(low)) produced IFN-γ, IL-4, and IL-17, thus, considered to be immune effector T cells (Teff). Significantly more Teff numbers were detected in LD-SCLC patients than that of extended-stage SCLC (ED-SCLC). By contrast, induction of CD62L^(high) CD25^+ CD4^+ Treg was significantly higher in ED-SCLC patients than that of LD-SCLC patients. Analyses of cytokine secretion revealed that Teff in LD-SCLC patients produced significantly more IL-17 and that dendritic cells derived from CD14^+ cells of LD-SCLC patients secreted more IL-23. Long-term survivors of SCLC maintained a high Teff to Treg ratio, whereas patients with recurrent disease exhibited a low Teff to Treg ratio. Therefore, we concluded 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 effector CD4^+ T cells, particularly Th17 cells, while eliminating Treg to control systemic dissemination of SCLC.
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