2022 Fiscal Year Final Research Report
Mechanisms of Antibody Drug Resistance in Pancreatic Cancer: Focus on Complement Regulatory Proteins.
Project/Area Number |
20K16419
|
Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
|
Research Institution | Fukushima Medical University |
Principal Investigator |
Suzuki Rei 福島県立医科大学, 医学部, 助教 (80590546)
|
Project Period (FY) |
2020-04-01 – 2023-03-31
|
Keywords | 膵癌 / 補体 / C3a受容体 |
Outline of Final Research Achievements |
Our findings include the followings. First, we found that C3AR (complement component 3a receptor) is expressed in pancreatic cancer cells. Adding its ligand, C3a, enhances cell proliferation and invasion. Second, we also identified the presence of C3 protein within the cytoplasm of pancreatic cancer cells, which is involved in epithelial-mesenchymal transition, a process associated with cancer metastasis. Finally, we found that C3AR expression promotes the infiltration of immune cells, particularly M2 macrophages and regulatory T cells. 4) C3AR is involved in M2 macrophage polarization, known to suppress anti-tumor immune responses. Decreased C3AR expression inhibits M2 polarization and promotes the activation of cytotoxic T cells. These findings highlight the significance of C3AR in pancreatic cancer progression and suggest its potential as a target for reversing immune suppression and enhancing anti-cancer immune responses.
|
Free Research Field |
消化器内科
|
Academic Significance and Societal Importance of the Research Achievements |
膵癌細胞に発現する補体C3や受容体C3ARとEMTに関する報告はなく新規性高い報告となった。新規の抗がん薬開発が進まない膵癌治療において、C3ARは新たな治療標的となる可能性がある。また、抗腫瘍免疫応答において免疫抑制的に作用するM2マクロファージの発生においてもC3ARが関連している可能性がある事は大変興味深い。C3ARを標的とする治療が膵癌細胞のEMTを抑制できるだけではなく、同時に免疫抑制細胞の作用を減弱させる抗腫瘍免疫応答増強にも寄与できる可能性があると考えた。
|