Radiation and immune checkpoint inhibition for the treatment of advanced rectal cancer with distant micrometastasis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10649
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Jichi Medical University
• Principal Investigator: Horie Hisanaga 自治医科大学, 医学部, 教授 (20316532)
• Co-Investigator(Kenkyū-buntansha): 北山 丈二 自治医科大学, 医学部, 教授 (20251308) ; 鯉沼 広治 自治医科大学, 医学部, 准教授 (20382905) ; 山口 博紀 自治医科大学, 医学部, 教授 (20376445) ; 井上 賢之 自治医科大学, 医学部, 講師 (80375279)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 直腸癌 / 肺転移 / 放射線治療 / CD73 / 接着 / Abscopal effect

Outline of Final Research Achievements

LuM-1, a highly metastatic murine colon cancer, expresses CD73 with significantly enhanced expression after RT. Selective RT suppressed the growth of the irradiated sc tumor, but did not affect the growth of lung metastases which were shielded from RT. Anti-CD73 antibody alone did not produce antitumor effects. However, when combined with RT anti-CD73 further delayed the growth of sc tumors and suppressed the development of lung metastases presumably through abscopal effects. Splenocytes derived from RT+ anti-CD73 treated mice showed enhanced IFN-gamma production.
Immunohistochemical studies of irradiated human rectal cancer showed that high expression of CD73 in remnant tumor cells and/or stroma is significantly associated with worse outcome.
Adenosine plays an important role in the anti-tumor effects mediated by RT and that CD73/adenosine axis blockade may enhance the anti-tumor effect of RT, and improve the outcomes of patients with locally advanced rectal cancer.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

直腸癌の術前放射線療法にCD73阻害抗体による免疫療法を付加することで、照射腫瘍だけでなく、Abscopal effectを介して遠隔転移の成長をも抑制する効果が得られることが動物実験で明らかになった。また、ヒト標本でのCD73の発現が予後と関連することが証明され、今後の進行直腸癌に対する術前療法を考える上で重要な基礎的知見が得られた。