Pancreatic-biliary tract cancer treatment with an anti-tumor T cell activation through inhibition of tumor-promoting macrophages

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K19866
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Hirosaki University
• Principal Investigator: Miura Takuya 弘前大学, 医学部附属病院, 講師 (30722136)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 腫瘍促進TAM / 抗腫瘍T細胞 / TLR3

Outline of Final Research Achievements

In the patients with extrahepatic bile duct cancer, the histopathological analysis demonstrated high infiltration of tumor-promoting macrophages and low infiltration of tumor-killing T-cells have a poor prognostic impact. In vitro research was conducted on pancreatic and biliary cancer, but the prospect of the experimental design was out of order. Considering feasible research from the cooperation system in our institution, we focused on TLR3. Tumor cells are known to undergo necrosis due to external stress such as chemotherapy and radiation therapy. In this situation, endogenous factors called DAMPs are thought to work in tumor promotion or suppression via TLR3 in tumor microenvironment. In this research, TLR3 expression in tumor cells is associated with lymph node metastasis and induces expression of CCL2, CCL5, and IL-8. Tumor cell expression of TLR3 is suggested to affect surrounding microenvironment and to be related to metastatic potential.

Free Research Field

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Academic Significance and Societal Importance of the Research Achievements

腫瘍促進TAMを標的とし、抗腫瘍T細胞浸潤を調節することで予後の改善が期待できることを示唆した一方、TLR3という免疫機構に関連するシステムが腫瘍細胞に存在し、それが腫瘍微小環境に影響を与え、腫瘍の進展に寄与することを示唆したことが研究成果である。この知見は、宿主に存在する免疫機構の中心的存在であるマクロファージやT細胞を標的とする場合、それらの免疫機構を調節することは、腫瘍細胞にも影響を及ぼす事実を示している。腫瘍免疫の複雑系を示唆し、微小環境を標的とする際、腫瘍細胞自体にも着目する必要があることを示したことに社会的意義がある。