| Project/Area Number |
20591326
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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 |
Dermatology
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| Research Institution | Jichi Medical University |
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Principal Investigator |
MURAKAMI Takashi Jichi Medical University, 医学部, 准教授 (00326852)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | メラノーマ / 免疫抑制 / 養子細胞移入療法 / 未熟骨髄由来細胞 / ケモカイン |
|---|
| Research Abstract |
With melanoma, as with many other malignancies, the immune-suppressive tumor microenvironment is a hallmark of cancer and a major obstacle to immune therapy. Myeloid-derived suppressor cells (MDSCs) contribute to immune dysfunctions induced by tumors both in experimental models and patients. While CD11b^+Gr1^+ myeloid cells are well-known markers for MDSCs in mice, only a limited number of literatures have been reported for drastic mobilization of CD11b^+Gr1^+ MDSCs in B16 melanoma-bearing C57BL/6 mice. To seek out mobilizing conditions of CD11b^+Gr1^+ MDSCs in C57BL/6 mice, the population size of CD11b^+Gr1^+ cells was investigated using some immunodeficient mice. Mobilization of CD11b^+Gr1^+ cells of B16 melanoma-bearing and melanoma-free mice was assessed by flow cytometric analysis. Moreover, achievement in mobilization of CD11b^+Gr1^+ cells was also evaluated using mice that formed interleukin (IL)-4-expressing B16 melanoma tumor. B16 melanoma in C57BL/6 wild-type mice less mobilizes CD11b^+Gr1^+ myeloid cells, but CD11b^+Gr1^+ cells were significantly mobilized in Rag1-/- and Tbx-/- mice that lack T and B cells and Th1-type immune response, respectively. Furthermore, IL-4-expressing B16 melanoma-bearing mice facilitated mobilization of CD11b^+Gr1^+ MDSCs in those immunodeficient mice in concomitant with the decrease of F4/80^+ macrophages. Furthermore, we found that the latest member of the C-X-C-type chemokines, CXCL17 (DMC/VCC-1), recruited immature myeloid-derived cells and enhances early tumor progression. Our data suggest that aberrant expression of CXCL17 in tumor cells recruits immature myeloid-derived cells and promotes early tumor progression through angiogenesis.
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