Gene alterations and anti-tumor immunity

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K18388
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology; Respiratory organ internal medicine
• Research Institution: National Cancer Center Japan
• Principal Investigator: Togashi Yosuke 国立研究開発法人国立がん研究センター, 先端医療開発センター, 研究員 (80758326)
• Research Collaborator: Tsuboi Masahiro ; Shitara Kohei
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: がん免疫 / ゲノム異常 / 非小細胞肺癌 / 体細胞変異数 / EGFR遺伝子変異 / 胃癌

Outline of Final Research Achievements

We investigated immunological phenotypes in tumor microenvironment (TME) of EGFR-mutated lung adenocarcinomas, to which cancer immunotherapy is largely ineffective. While EGFR-mutated lung adenocarcinomas had non-inflamed tumor micronenvironment, CD4+ effector regulatory T cells (Tregs), that are highly infiltrated. The EGFR signal plays an important role in this unique tumor micronenvironment and an EGFR signal inhibitor improved the immune status, and combination with immunotherapy provided better anti-tumor effects compared with either of single treatment.
Furthermore, we investigated gene signature related to Treg-infiltration, showing a specific gene signature. We further analyze this relationship.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

がんの遺伝子異常、特に従来は細胞の増殖や生存に深く関わるとされてきたようなドライバー遺伝子異常が、積極的にがんの周囲の免疫状態をコントロールして、がんにとって有利な環境を作り出していることが明らかとなった。これらの遺伝子異常を標的にするような薬剤とがん免疫療法を併用することで、今までは効果があまりなかった症例に対しても効果を発揮できる可能性がある。