Elucidation of molecular mechanisms of and development of combined therapy with immune checkpoint inhibitors for digestive tract cancer
| Project/Area Number |
16K10502
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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 |
Digestive surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
北尾 洋之 九州大学, 薬学研究院, 教授 (30368617)
沖 英次 九州大学, 大学病院, 講師 (70380392)
中島 雄一郎 九州大学, 医学研究院, 助教 (40733564)
杉山 雅彦 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 消化管外科医師 (40751079)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 食道扁平上皮癌 / 集学的治療 / 免疫チェックポイント阻害剤 / 消化管外科 / トランスレーショナルリサーチ / マイクロサテライト不安定性 / 免疫チェック ポイント阻害剤 / 抗腫瘍免疫 / 癌集学的治療 |
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| Outline of Final Research Achievements |
170 patients without neoadjuvant therapy and 71 patients with neoadjuvant chemotherapy for esophageal squamous cell carcinoma, who underwent curative esophagectomy, were included in present study. Compared with the patients without neoadjuvant chemotherapy, PD-L1 expression in those with neoadjuvant chemotherapy was significantly higher on both tumor and interstitial cells (p<0.01 and p<0.05, respectively). CD68-positive cells were also recognized more in the microenvironment of neoadjuvant chemotherapy group than in that of no neoadjuvant therapy group (p<0.05). It was revealed that CD68-positive cells significantly correlated with PD-L1 expression on tumor cells in the patients with neoadjuvant chemotherapy (p<0.01). On the other hand, the correlation wasn’t recognized in the group without neoadjuvant chemotherapy (p=0.22). The differences about HLA class I expression was not recognized and CD8 positive cells were fewer in neoadjuvant chemotherapy group.
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| Academic Significance and Societal Importance of the Research Achievements |
免疫チェックポイント関連分子のPD-L1は、腫瘍細胞のみならず、マクロファージを含む免疫細胞でも発現しており、それらのPD-L1発現は、化学療法などで修飾を受ける可能性が複数の癌種で報告されている。本研究の結果、NAC後の食道扁平上皮癌では、腫瘍細胞と免疫細胞におけるPD-L1発現は亢進しており、一方で腫瘍のPD-L2発現は低下していた。またCD8リンパ球数は減少していたが、マクロファージ数は増加していた。今後NAC後の免疫細胞におけるPD-L1発現増加とマクロファージ増加の関連の検討を進めていくことで、食道扁平上皮癌に対する新規治療戦略の開発が期待できる。
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Report
(4 results)
Research Products
(38 results)
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[Journal Article] Prophylactic Effect of Dexamethasone on Regorafenib-Related Fatigue and/or Malaise: A Randomized, Placebo-Controlled, Double-Blind Clinical Study in Patients with Unresectable Metastatic Colorectal Cancer (KSCC1402/HGCSG1402).2018
Author(s)
Tanioka H, Miyamoto Y, Tsuji A, Asayama M, Shiraishi T, Yuki S, Kotaka M, Makiyama A, Shimokawa M, Shimose T, Masuda S, Yamaguchi T, Komatsu Y, Saeki H, Emi Y, Baba H, Oki E, Maehara Y; Kyushu Study Group of Clinical Cancer (KSCC).
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Journal Title
Oncology.
Volume: 94(5)
Issue: 5
Pages: 289-296
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinicopathological features of cervical esophageal cancer: Retrospective analysis of 63 consecutive patients who underwent surgical resection.2017
Author(s)
Saeki H, Tsutsumi S, Yukaya T, Tajiri H, Tsutsumi R, Nishimura S, Nakaji Y, Kudou K, Akiyama S, Kasagi Y, Nakashima Y, Sugiyama M, Sonoda H, Ohgaki K, Oki E, Yasumatsu R, Nakashima T, Morita M, Maehara Y
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Journal Title
Ann Surg
Volume: 265
Issue: 1
Pages: 130-136
DOI
Related Report
Peer Reviewed
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[Journal Article] Prognostic Significance of Postoperative Complications after Curative Resection for Patients with Esophageal Squamous Cell Carcinoma.2017
Author(s)
Saeki H, Tsutsumi S, Tajiri H, Yukaya T, Tsutsumi R, Nishimura S, Nakaji Y, Kudou K, Akiyama S, Kasagi Y, Nakanishi R, Nakashima Y, Sugiyama M, Ohgaki K, Sonoda H, Oki E, Maehara Y:
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Journal Title
Annals of Surgery
Volume: 265
Issue: 3
Pages: 527-33
DOI
Related Report
Acknowledgement Compliant
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[Journal Article] Current status of and perspectives regarding neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma2015
Author(s)
Saeki H, Nakashima Y, Zaitsu Y, Tsuda Y, Kasagi Y, Ando K, Imamura Y, Ohgaki K, Ito S, Kimura Y, Egashira A, Oki E, Morita M, Maehara Y
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Journal Title
Surg Today
Volume: Mar 5. [Epub ahead of print]
Issue: 3
Pages: 261-7
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] “Energy-less technique” with mini-clips for recurrent laryngeal nerve lymph node dissection in prone thoracoscopic esophagectomy for esophageal cancer2018
Author(s)
Hiroshi Saeki, Yuichiro Nakashima, Nobuhide Kubo, Kosuke Hirose, Shun Sasaki, Tomoko Jogo, Daisuke Taniguchi, Keitaro Edahiro, Shotaro Korehisa, Ryota Nakanishi, Koji Ando, Eiji Oki, Yoshihiko Maehara
Organizer
16th World Congress, International Society for Diseases of the Esophagus
Related Report
Int'l Joint Research
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