Immune cytolytic activity to assess anti-tumor immunity associates with intra-tumoral genetic heterogeneity and impacts clinical outcomes in solid tumor

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21289
• Project/Area Number (Other): 18H06184 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0901:Oncology and related fields
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: KAWAGUCHI TSUTOMU 京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (60825058)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 腫瘍免疫 / ゲノム / 乳癌 / 肝臓癌 / 免疫微小環境 / シーケンス

Outline of Final Research Achievements

Our aim was to examine the immune landscape of BrCa as it relates to aspects of tumor biology, including intra-tumoral genetic heterogeneity and clinical significance. Using The Cancer Genome Atlas (TCGA) and other large independent datasets, we correlated cytolytic activity (CYT) with mutational, structural, and genetic features of the tumor, as well as clinical outcomes. High CYT associates with high anti-tumor immunity and genetic heterogeneity, suggesting that intrinsic oncogenic processes strongly correlated with intra-tumoral immune landscape. Furthermore, cytolytic activity combined with PD-L1 status may provide an improved index predicting the clinical outcomes in BrCa patients.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

本研究はさらなる革新的な網羅的ゲノム解析手法の導入により、固形癌の転移浸潤における免疫微小環境の役割とその臨床的意義の解明を目的とした。従来の腫瘍を分割して複数の解析をする手法と異り、本研究では単一のシーケンスデータから複数のパラメターを計測、独自に開発した数理モデル解析基盤を適応した。すなわち、革新的なトランスクリプトミクスレベルの解析アルゴリズムを応用し、腫瘍内の免疫微小環境を定量、評価する。またDNA シーケエンスデータを元に腫瘍内のゲノム不安定性を定量した。本手法は他の様々な癌種の免疫微小環境を含めた病態解明さらには適切な治療法の確立に寄与すると考えられる。