Identification of molecules recognized by invariant NKT cells independently of CD1d

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17408
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Chiba University (2022); Institute of Physical and Chemical Research (2020)
• Principal Investigator: Aoki Takahiro 千葉大学, 大学院医学研究院, 助教 (30791553)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: NKT細胞 / NK受容体 / CRISPRライブラリー

Outline of Final Research Achievements

Invariant NKT cells are known to recognize tumor cells by detecting glycolipids presented on CD1d through their T cell receptor (TCR). However, the identity of other molecules involved in tumor recognition remains unknown. Therefore, the objective of this study was to identify tumor recognition molecules that function independently of CD1d, using induced pluripotent stem cell-derived NKT cells (iPS-NKT cells). These iPS-NKT cells were able to recognize CD1d-negative tumors in a TCR-independent manner. NK receptors expressed on iPS-NKT cells were identified using mass cytometry, and target molecules expressed on tumor cells were identified by a CRISPR library.

Free Research Field

がん免疫

Academic Significance and Societal Importance of the Research Achievements

本研究でiPS-NKT細胞は今回同定したNK受容体とそのリガンドを介して、CD1d非依存性にも腫瘍認識し、細胞傷害活性を発揮することを明らかにした。このことはiPS-NKT細胞療法がCD1d発現がん細胞に限定されることなく、当リガンドを発現するがん種にも有効であることを示唆する。