Development of chemo-immunotherapy based on the characterization of tumor-infiltrating myeloid-derived suppressor cells
| Project/Area Number |
16K08752
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Aoki Kazunori 国立研究開発法人国立がん研究センター, 研究所, 分野長 (60270675)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 化学免疫療法 / 骨髄由来抑制細胞 / サイトカイン / シングルセル解析 / 肺がん / 間質線維芽細胞 / 免疫学 |
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| Outline of Final Research Achievements |
To develop the effective chemo-immunotherapy, we focused on the characterization of tumor-infiltrating myeloid-derived suppressor cells (MDSC), which are considered as a major resistance factor against the antitumor induction by chemo-immunotherapy.
We identified a specific subtype in tumor-infiltrating MDSCs and elucidated the characteristics of the gene expression profile. Then, we found that the cancer-associated fibroblasts recruited the MDSC into tumors by production of MDSC-related cytokines such as CXCL6. Finally, we showed that the combination of chemotherapy and the depletion of MDSC enhanced antitumor immunity and induce synergistic antitumor effect in mouse model.
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| Academic Significance and Societal Importance of the Research Achievements |
免疫チェックポイント阻害剤が多くのがん種に対して有効性を示すが、70-80％が抵抗性を示す。そこで、現在、化学療法と免疫療法の併用などの複合的免疫療法の開発が期待されている。
本研究では、化学免疫療法の抵抗因子である骨髄由来抑制細胞(MDSC)に着目して、腫瘍内に浸潤する特徴的なサブタイプを同定、またMDSCの腫瘍への浸潤機構を明らかとした。さらに、MDSCを抑制することにより化学免疫療法の効果が増強できることを示した。これらの研究成果は、今後有効な化学免疫療法の開発に結びつけるうえでの重要な基礎データとなる。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] The peripheral immune status of granulocytic myeloid-derived suppressor cells correlates the survival in advanced gastric cancer patients receiving cisplatin-based chemotherapy2017
Author(s)
Shoji H, Heike Y, Tada K, Kitano S, Nishimura T, Shimada Y, Nagashima K, Aoki K, Hiraoka N, Honma Y, Iwasa S, Takashima A, Kato K, Boku N, Honda K, Yamada T, Hamaguchi T.
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Journal Title
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pretreatment Immune Status Correlates with Progression-Free Survival in Chemotherapy-Treated Metastatic Colorectal Cancer Patients.2016
Author(s)
Tada K, Kitano S, Shoji H, Nishimura T, Shimada Y, Nagashima K, Aoki K, Hiraoka N, Honma Y, Iwasa S, Okita N, Takashima A, Kato K, Yamada Y, Katayama N, Boku N, Heike Y, Hamaguchi T.
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Journal Title
Cancer immunology research
Volume: 4(7)
Issue: 7
Pages: 592-599
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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