Mobilization of myeloid-derived suppressor cells in the melanoma progression and the study of the effective adoptive immunotherapy
| 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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Report
(4 results)
Research Products
(54 results)
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[Journal Article] Profile of new green fluorescent protein (GFP)-transgenic Jinhua pigs as an imaging source.2009
Author(s)
Kawarasaki T, Uchiyama K, Hirao A, Azuma S, Otake M, Shibata M, Tsuchiya S, Enosawa S, Takeuchi K, Konno K, Yoshino H, Hakamata Y, Wakai T, Ookawara S, Tanaka H, Kobayashi E, Murakami T.
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Journal Title
J Biomed Opt 14(5)
Pages: 54017-54017
Related Report
Peer Reviewed
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