A research for new bladder preservation therapy by combination of radiation therapy with immune checkpoint inhibitors

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10467
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: University of Tsukuba
• Principal Investigator: Ishikawa Hitoshi 筑波大学, 医学医療系, 教授 (70344918)
• Co-Investigator(Kenkyū-buntansha): 松本 孔貴 筑波大学, 附属病院, 病院助教 (70510395)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 免疫チェックポイント阻害剤 / 腫瘍免疫 / 膀胱癌 / 放射線治療

Outline of Final Research Achievements

A clinical study, testing the efficacy of immunity checkpoint inhibitor and radiotherapy (RT) for bladder cancer, has been planned, and results of a literature review and a planned protocol were submitted to the international journals. The study has been started since January, 2019, and 14 patients were registered by March, 2020. An additional study to explore molecular markers predicting outcomes was also initiated.
The mice B16 cell lines, which induced PD-L1 expression by RT, were analyzed to explore effective combination of RT with immune checkpoint inhibitors.　Upregulations of IFN-gamma and GM-CSF by RT were correlated with the local control. When the inhibitors were given just after RT, the enhance ratio was the maximum. A correlation of molecular markers such as p53, STAT3, NF-kB, and PD-L1 expressions in addition to the Rho-ROCK signal pathway with treatment outcomes in the bladder cancer have being examined.

Free Research Field

放射線医学

Academic Significance and Societal Importance of the Research Achievements

浸潤性膀胱癌の標準治療は外科治療であるが、その侵襲性だけでなく、尿路変更が必要となるため患者のQOLを大きく損なう。膀胱を温存する根治療法としてTrimodalityが最近注目されてきているが、放射線治療に併用される薬物治療は抗がん剤が中心である。
近年、分子生物学、腫瘍免疫学の著しい進歩によって、放射線治療による腫瘍免疫の賦活化が注目され、遠隔転移を有する症例の姑息療法だけでなく、進行肺癌の根治療法としても免疫チェックポイント阻害剤と放射線治療の併用が標準治療として行われる時代になった。本研究は高齢や腎機能低下のある症例に対しても忍容性の高い新規膀胱温存療法の開発に貢献できると考える。