CRISPR/Cas9 genome-wide knockout screening for identifying the novel gene to overcome the tumor-immune escape

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07695
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Osaka University
• Principal Investigator: Morimoto Soyoko 大阪大学, 大学院医学系研究科, 寄附講座助教 (10649023)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: CRISPR-guide RNA library / Cas9 / CD8T cell

Outline of Final Research Achievements

Genome-wide knockout screening using CRISPR-guide RNA library/Cas9 system identified the novel gene X to maintain the expression of CD27 in CD8T cells under conditions that reduce CD27 expression. Repression of gene X expression promoted proliferation and remained cytokine production and cytotoxicity in addition to retaining CD27 expression in CD8T cells. To clarify the proliferation mechanism, now we analyze and integrate information of ATAC-seq and RNA-seq between control-CD8T cells and gene X-repressed CD8T cells.

Free Research Field

癌免疫

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害療法やCAR-T細胞療法は、強力な抗腫瘍効果が期待できる癌免疫療法である。しかしながら、腫瘍攻撃の中核を担う細胞傷害性T細胞の「品質」の低下が原因で、治療を受けた患者のすべてに強い抗腫瘍効果が発揮されるわけではない。強い細胞傷害活性と高い増殖能は、T細胞に本来備わっている性質としては同時に成立しない。そこで、本研究成果で得られた「細胞傷害活性の維持と驚異的な増殖能を発揮する癌抗原特異的T細胞」は、現在の癌免疫療法が直面する最大の課題を解決することが大いに期待される。