Elucidation of immune checkpoint regulatory mechanisms and development of novel therapies

2022 Fiscal Year Final Research Report

• Project/Area Number: 22K20798
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Yokohama City University
• Principal Investigator: KAMIMAKI Chisato 横浜市立大学, 附属病院, 助教 (80965715)
• Project Period (FY): 2022-08-31 – 2023-03-31
• Keywords: 免疫チェックポイント

Outline of Final Research Achievements

We added gemcitabine and a control anticancer drug that did not affect TIM3 expression to human PBMCs and obtained RNA-seq data (unpublished in 2022). From this data, we examined genes that were differentially expressed by the anticancer drugs and picked up several genes and ncRNAs, including miR-1254 and JUN. In particular, JUN was found to be differentially expressed by Western blotting when PBMCs were treated with anti-cancer drugs, and the relationship between the protein expression and TIM3 expression was confirmed by flow cytometry with JUN inhibitor.

Free Research Field

肺癌

Academic Significance and Societal Importance of the Research Achievements

肺癌は癌による死亡者数で最多であり、治療成績の向上が求められている。肺癌の薬物療法は、免疫チェックポイント阻害薬（ICI）が標準治療となったが、ICI耐性への対応という課題が発生した。免疫チェックポイントにはPD-1以外にもLAG3、TIM3、TIGIT等複数存在しており、本研究ではTIM3に着目して肺癌で使用される殺細胞性抗癌剤の種類によってこのTIM3発現に影響を与える可能性が示唆された。