Elucidation of the hypoxic immune response and its application to multidisciplinary therapy
Project/Area Number |
16H05415
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Kobe University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
青井 貴之 神戸大学, 科学技術イノベーション研究科, 教授 (00546997)
佐々木 良平 神戸大学, 医学部附属病院, 教授 (30346267)
鈴木 知志 神戸大学, 医学研究科, 特命教授 (30457080)
岡田 誠治 熊本大学, ヒトレトロウイルス学共同研究センター, 教授 (50282455)
山下 公大 神戸大学, 医学部附属病院, 特命准教授 (80535427)
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
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Keywords | 術前治療 / 低酸素 / 腫瘍免疫微小環境 / CD8+T細胞 / iPS細胞 / CD8+T細胞 / iPS技術 / 免疫応答 / CD8+細胞 / iPS / CD8+細胞 |
Outline of Final Research Achievements |
We investigated the effects of preoperative therapy on the tumor immune microenvironment in esophageal cancer surgery after preoperative chemotherapy and rectal cancer surgery after preoperative chemoradiotherapy. We showed the prognostic impact of the expression levels of immune-related molecules. Besides, we created a radiation mouse model using the CT26 colorectal cancer cell line. We found that intratumoral T cells were markedly increased after radiotherapy. Many of these T cells were PD-1+Tim-3+, suggesting a significant increase in tumor-reactive T cells. We want to investigate the mechanism of this change and use it to improve surgical outcomes during preoperative treatment.
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Academic Significance and Societal Importance of the Research Achievements |
低酸素環境下の腫瘍微小環境の変化は治療抵抗性を獲得する特性であるが、これは同時に正常細胞の酸素供給の変化に対するホメオスターシスの維持に必要な応答である。放射線・化学療法下では免疫細胞も低酸素に応答する。低酸素に対する免疫細胞の応答の解析は学術的意義は深い。これを利用した治療介入により術前・術後治療を開発しようとするユニークな研究である。現在、臨床現場で使用可能な免疫学的治療の介入機会を明らかにし、術前・術後補助治療を改良し、治療成績の向上をめざすことは、癌の根治性に繋がり、意義深い研究と言える。
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Report
(5 results)
Research Products
(57 results)
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[Journal Article] miR-221 Targets QKI to Enhance the Tumorigenic Capacity of Human Colorectal Cancer Stem Cells.2019
Author(s)
Mukohyama J, Isobe T, Hu Q, Hayashi T, Watanabe T, Maeda M, Yanagi H, Qian X, Yamashita K, Minami H, Mimori K, Sahoo D, Kakeji Y, Suzuki A, Dalerba P, Shimono Y.
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Journal Title
Cancer Research
Volume: 79
Issue: 20
Pages: 5151-5158
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Neoadjuvant Chemotherapy Increases PD-L1 Expression and CD8(+) Tumor-infiltrating Lymphocytes in Esophageal Squamous Cell Carcinoma.2019
Author(s)
Fukuoka E, Yamashita K, Tanaka T, Sawada R, Sugita Y, Arimoto A, Fujita M, Takiguchi G, Matsuda T, Oshikiri T, Nakamura T, Suzuki S, Kakeji Y.
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Journal Title
Anticancer Research
Volume: 39
Issue: 8
Pages: 4539-4548
DOI
Related Report
Peer Reviewed
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[Journal Article] 3D Culture Represents Apoptosis Induced by Trastuzumab Better than 2D Monolayer Culture2018
Author(s)
Tatara T, Mukohara T, Tanaka R, Shimono Y, Funakoshi Y, Imamura Y, Toyoda M, Kiyota N, Hirai M, Kakeji Y, Minami H.
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Journal Title
Anticancer Res
Volume: 38
Issue: 5
Pages: 2831-2839
DOI
Related Report
Peer Reviewed
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[Journal Article] Application of iNKT Cell-targeted Active Immunotherapy in Cancer Treatment.2018
Author(s)
Yamashita K, Arimoto A, Nishi M, Tanaka T, Fujita M, Fukuoka E, Sugita Y, Nakagawa A, Hasegawa H, Suzuki S, Kakeji Y.
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Journal Title
Anticancer Research
Volume: 38
Issue: 7
Pages: 4233-4239
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Outcomes and prognostic factors of selective lateral pelvic lymph node dissection with preoperative chemoradiotherapy for locally advanced rectal cancer.2018
Author(s)
Matsuda T, Sumi Y, Yamashita K, Hasegawa H, Yamamoto M, Matsuda Y, Kanaji S, Oshikiri T, Nakamura T, Suzuki S, Kakeji Y.
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Journal Title
Int J Colorectal Dis.
Volume: 33
Issue: 4
Pages: 367-374
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Expression of programmed death-1 in sentinel lymph nodes of breast cancer.2017
Author(s)
Tatara T, Mukohara T, Shimono Y, Yamasaki T, Imamura Y, Funakoshi Y, Toyoda M, Kiyota N, Takao S, Kono S, Kakeji Y, Minami H
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Journal Title
J Surg Oncol.
Volume: Epub ahead of print
Issue: 6
Pages: 2017-2017
DOI
Related Report
Peer Reviewed
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[Journal Article] Frequency of Myeloid-derived Suppressor Cells in the Peripheral Blood Reflects the Status of Tumor Recurrence.2017
Author(s)
Tanaka T, Fujita M, Hasegawa H, Arimoto A, Nishi M, Fukuoka E, Sugita Y, Matsuda T, Sumi Y, Suzuki S, Kakeji Y, Yamashita K
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Journal Title
Anticancer Res.
Volume: 37
Pages: 3863-3869
Related Report
Peer Reviewed / Open Access
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[Journal Article] CXCL8 derived from tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression by promoting migration and invasion of cancer cells.2017
Author(s)
Hosono M, Koma Y, Takase N, Urakawa N, Higashino N, Suemune K, Kodaira H, Nishio M, Shigeoka M, Kakeji Y, Yokozaki H
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Journal Title
Oncotarget
Volume: 8
Issue: 62
Pages: 106071-106088
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prognostic significance of pathological response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer2016
Author(s)
Tomono A, Yamashita K, Kanemitsu K, Sumi Y, Yamamoto M, Kanaji S, Imanishi T, Nakamura T, Suzuki S, Tanaka K, Kakeji Y
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Journal Title
Int J Clin Oncol
Volume: 21
Issue: 2
Pages: 344-49
DOI
Related Report
Peer Reviewed
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[Presentation] Mukohyama J,Shimono Y,Dalerba P,Isobe T,Hu Q,Sahoo D,Shibuya N,Minami H,Mimori K,Kakeji Y,Suzuki A2018
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[Presentation] The induction of PD-L1 positive immune cells and CD8-positive T lymphocytes by neoadjuvant chemoradiotherapy for rectal cancer2018
Author(s)
Yamashita K,Nakagawa A,Tanaka T,Arimoto A,Fukuoka E,Sugita Y,Mukoyama J,Dalerba P,Hasegawa H,Matsuda T,Suzuki S,Kakeji Y
Organizer
AACR Annual Meeting 2018
Related Report
Int'l Joint Research
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[Presentation] Outcomes and prognostic factors of selective lateral pelvic lymph node dissection with preoperative chemoradiotherapy for locally advanced rectal cancer2017
Author(s)
Fukuoka E,Matsuda Y,Sumi Y,Yamashita K,Hasegawa H,Yamamoto M,Matsuda T,Kanaji S,Oshikiri T,Nakamura T,Suzuki S,Kakeji Y
Organizer
日本・モンゴル国際消化器がんシンポジウム
Related Report
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