Elucidation of the mechanism of cancer immune environment modification by chemotherapy using scRNA-seq

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22957
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0905:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Kyushu University
• Principal Investigator: ANDO Yohei 九州大学, 医学研究院, 共同研究員 (40746864)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: scRNA-seq / 消化器癌 / 化学療法 / 免疫微小環境

Outline of Final Research Achievements

We collected tumors from gastric cancer patients who had undergone gastrectomy and then used scRNA-seq to evaluate function-related gene expression of immune cells changed by preoperative chemotherapy (NAC). CD8-positive T cells in the NAC group showed significantly higher expression of cytotoxicity-related genes and substantially higher expression of exhaustion-related genes. The expression of immunosuppression-related genes was also significantly higher in gastric cancer cells and regulatory T cells in the NAC group.
Furthermore, we evaluated the tumor immune microenvironment altered by NAC in esophageal cancer and showed that NAC enhanced anti-tumor immune responses.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

胃癌に対する化学療法は免疫原性を高めると同時に、腫瘍は免疫回避機構として免疫抑制環境を形成していることが示唆され、これが治療耐性化の機序の一つである可能性が示唆された。本研究で明らかにしたNACによる腫瘍免疫微小環境の解明は、化学療法反応性のバイオマーカーや治療標的を検討する一助になると考えられた。