Elucidation of ACLP function in the head and neck cancer microenvironment and development of novel therapeutic strategies

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16846
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Yorozu Akira 札幌医科大学, 医学部, 訪問研究員 (20792120)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腫瘍微小環境 / がん関連線維芽細胞 / 細胞外基質 / 腫瘍微小免疫環境

Outline of Final Research Achievements

To analyze ACLP in cancer fibroblasts (CAFs), we performed functional analysis using CAFs collected from clinical specimens of squamous cell carcinoma of the head and neck. First, we found that ACLP is involved in the activation of CAFs, such as cell contraction and gel contractility, and in collagen secretion. We found that CAF-derived ACLP promotes migration and invasive ability of cancer cells via epithelial-mesenchymal transition and enhances CDDP resistance. Furthermore, in an experimental system in which cancer cells were co-cultured with CAFs in which ACLPs were knocked down, it was shown that CAF-derived ACLPs may inhibit the recruitment of CD8+ T cells to tumor cells. Future studies will focus on the role of CAF and ACLP in the tumor microimmune environment.

Translated with DeepL.com (free version)

Free Research Field

腫瘍微小環境

Academic Significance and Societal Importance of the Research Achievements

腫瘍は増大する際に腫瘍間質を形成するが、この機能的意義については明らかになっていない。我々はACLPという分泌タンパクに注目して腫瘍間質細胞の働きに注目して研究を行ってきた。ACLPは腫瘍間質細胞から分泌され、癌細胞に対しては癌細胞の遊走・浸潤能を亢進することで腫瘍促進的に働くことを明らかにした。また腫瘍免疫に重要なCD8陽性T細胞に対してはACLPを分泌を介してT細胞の腫瘍内浸潤を阻害するという腫瘍免疫抑制に働く可能性を示した。このようにACLPは腫瘍腫瘍間質を細胞に発現し多機能的に腫瘍を促進するポテンシャルを持ったタンパクであることが明らかになった。