• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2022 Fiscal Year Final Research Report

The mechanistic analyses of modulation of Tumor microenvironment by characteristic metabolite released from NRF2-addicted cancer cells

Research Project

  • PDF
Project/Area Number 19K07379
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49010:Pathological biochemistry-related
Research InstitutionTohoku Medical and Pharmaceutical University (2021-2022)
Tohoku University (2019-2020)

Principal Investigator

Kitamura Hiroshi  東北医科薬科大学, 医学部, 助教 (20706949)

Project Period (FY) 2019-04-01 – 2023-03-31
Keywords腫瘍免疫 / NRF2 / KEAP1 / 代謝物 / 肺がん
Outline of Final Research Achievements

Transcription factor NRF2 is constitutively activated by somatic mutation of KEAP1 or NFE2L2 genes in lung cancer, conferring the resistance against chemotherapy and radiotherapy to cancer cells. In order to clarify the mechanisms how persistent NRF2 activation contributes to cancer malignancy, we test the hypothesis that NRF2-activated cancer cells contribute to cancer malignancy by releasing immunosuppressive metabolite. First, NRF2-activated model cancer cells which is transplantable to C57BL6 mice is successfully established to analyze the immunosuppressive feature of tumor microenvironment. In addition to the result, specific features of NRF2-activated lung cancer patients are analyzed by the public available dataset and was found that certain types of immuno were drastically changed.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

NRF2依存性がん細胞は悪性腫瘍をしばしば形成しており、腫瘍微小環境に中において免疫細胞やがん繊維芽細胞の機能を調節しているかといった事については現在までに実験学的には証明されていなかった。近年の解析では、免疫チェックポイント阻害剤などに対しても抵抗性を示していることがヒト肺がんデータベースより明らかになっている。本研究ではこれらのメカニズムについて有用な知見を提供することができる点で、難治がんであるNRF2活性化がんの新たな治療標的の開発に繋がる研究となることが予想され、関連分野に波及するそのインパクトや効果は大きいと考えられる。

URL: 

Published: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi