Elucidation of the mechanism of cancer microenvironment regulation by renal cell carcinoma-specific exosomes focusing on neutrophils

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16694
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Osaka University
• Principal Investigator: Nakata Wataru 大阪大学, 医学系研究科, 招へい教員 (30648019)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 腎細胞癌 / エクソソーム / プロテオミクス / 好中球

Outline of Final Research Achievements

Based on the hypothesis that renal cell carcinoma-derived exosomal proteins are involved in T cell regulation, we identified 106 proteins that are significantly expressed in renal cell carcinoma-derived exosomes by proteomics. Caki-2 is a cell line that highly expresses both proteins, and we confirmed that exosomes derived from Caki-2 significantly suppress the proliferation of CD4-positive T cells. On the other hand, exosomes derived from other renal cancer cell lines with low expression of both proteins did not cause phenotypic changes. These results suggest that PAG1 and LAIR1 in exosomes derived from renal cell carcinoma may be involved in the suppression of CD4-positive T cell proliferation.

Free Research Field

癌免疫

Academic Significance and Societal Importance of the Research Achievements

我々は「腎細胞癌により、末梢血中免疫細胞の遺伝子発現プロファイルが変化する」、また、「腎細胞癌は癌特異的エクソソームを放出し、血管透過性を亢進する」こと、即ち腎細胞癌がエクソソームを介して癌微小環境を制御しうることを明らかにしてきた。近年、腎細胞癌に対する免疫療法が着目されているが、好中球に着目し腎癌細胞由来のエクソソームが免疫細胞の増殖を抑制し、エクソソームが今後免疫療法の効果を高めるための治療標的となりうること示した本研究の社会的意義は大きい。さらにプロテオミクスにより癌特異的なエクソソームタンパクを同定しており、今後さらにバイオマーカーへの応用や複合免疫療法開発など、臨床応用を目指す。