Development of novel immunotherapy for intestinal tumor targeting cell to cell contact between intestinal epithelial cell and intraepithelial lymphocyte

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20922
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0903:Organ-based internal medicine and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Morikawa Ryo 東京医科歯科大学, 東京医科歯科大学病院, 医員 (60910122)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: CD8αα / TL / CD103 / E-cadherin / 細胞間接触 / 腫瘍

Outline of Final Research Achievements

In order to evaluate importance of CD8αα/TL signal in anti- tumor immunity,
we applied anti-CD8αantibody derived from several clones to DPE-GFP mice, but there was no significant change in deposition of IEL. This result suggested that we can’t inhibit cell to cell contact between IEL-epithelial cell at least by neutralizing antibody we used in this experiment.
In order to examine usefulness of anti- tumor therapy by enhancing CD103/E-cadherin signal, we applied celecoxib which is thought to increase E-cadherin expression, to CD103-/- x APCmin and control mice. Tumor is decreased in the latter. However, there was trend that tumor is decreased also in the former, and anti-tumor effect was not fully canceled.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

我々はこれまでに、IELによる抗腫瘍活性はCD103及び細胞接触依存的である事、及びIEL特異的に発現するCD8ααがIELの高い運動能と上皮細胞間への配置に重要な役割を有する事を示してきた。
今回これらの研究を発展させ、CD103/E-cadherin及びCD8αα/TLシグナルを介したIEL-上皮細胞間相互作用を標的とした新規の腫瘍治療法の可能性を検討したが、今回の結果からはIEL-上皮細胞間接触を特異的に増強/阻害する系は特にin vivoでは困難と考えられた。今後はIEL-オルガノイド培養系を主軸に、EMT阻害剤等より特異性の高い薬剤のスクリーニングを検討し、新規標的の可能性を検討する。