Development of a novel immunotherapy for bladder cancer with SORL1 signaling and tumor immune microenvironment

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18126
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Toho University
• Principal Investigator: UTSUMI Takanobu 東邦大学, 医学部, 講師 (80594275)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 膀胱癌 / SORL1 / Cdc42 / 複合免疫療法 / PD-L1

Outline of Final Research Achievements

The behaviour of bladder cancer cells with and without SORL1 expression was studied in this study. It was observed that bladder cancer cells without SORL expression had increased migration and invasive capacity, increased Cdc42 and membrane MMP signalling, and formed invadopodia. Inhibition of SORL1-Cdc42 signalling with Cdc42 inhibitors reduced migration and invasive capacity and inhibited invadopodia formation, while targeted inhibition of Cdc42-N-WASP-Apr2/3 signalling in bladder cancer cells that do not express SORL1, This suppression of invadopodia formation was thought to reduce migration and invasive capacity, resulting in a therapeutic effect.

Free Research Field

泌尿器腫瘍

Academic Significance and Societal Importance of the Research Achievements

SORL1を発現しない膀胱癌ではCdc42-N-WASP-Apr2/3シグナルを標的として阻害することで、invadopodia形成抑制が起こり遊走能・浸潤能が低下して治療効果が現れると考えられた。また、SORL1の発現の有無によって、治療標的となるシグナルが判別できバイオマーカーとして可能性が示唆された。さらに、膀胱癌の細胞膜表面のPD-L1の発現をフローサイトメトリー法で確認しており、将来的に抗PD-1/PD-L1抗体療法とCdc42阻害剤との複合免疫療法の可能性が示唆された。