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2021 Fiscal Year Final Research Report

Development of novel therapeutic strategies for EGFR mutation-positive lung cancer by targeting semaphorin 7A

Research Project

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Project/Area Number 19K08602
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionOsaka University

Principal Investigator

Nagatomo Izumi  大阪大学, キャンパスライフ健康支援・相談センター, 教授 (10570583)

Project Period (FY) 2019-04-01 – 2022-03-31
Keywordsセマフォリン / がん免疫 / 肺癌薬物療法
Outline of Final Research Achievements

We have discovered a new mechanism of lung cancer antitumor immunity involving semaphorin 4A (SEMA4A) instead of the original target semaphorin 7A. Interleukin 33 (IL-33) induces semaphorin 4A expression in dendritic cells (DCs), resulting in activation of cytotoxic T cells (CTLs) and IFN-γ-mediated antitumor immune responses. This effect was not observed in SEMA4A knockout mice, demonstrating that SEMA4A is essential for the antitumor immunity by IL-33. The IL-33-induced, SEMA4A-mediated mutual activation of DCs and CTLs in the tumor microenvironment is a novel, previously unknown mechanism.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、肺癌においてインターロイキン33とセマフォリン4Aが抗腫瘍免疫にとって重要であることが証明された。また、これらの分子が治療標的となり得ること、及び、樹状細胞活性化状態のバイオマーカーとしても応用出来る可能性が示唆された。本研究で得られたデータを基に、ヒト肺癌患者においてもデータやサンプルを用いた解析を行い、臨床応用に向けて更に研究を進めていきたい。

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Published: 2023-01-30  

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