Novel biomarkers for the immune checkpoint inhibitors for cancer

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21250
• Project/Area Number (Other): 18H06135 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Kobayashi Koichi 北海道大学, 医学研究院, 教授 (60817162)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 免疫チェックポイント阻害剤 / NLRC5 / MHC class I / バイオマーカー

Outline of Final Research Achievements

We recently found that NLRC5/MHC class I transactivator (CITA) is a mastery transcriptional coactivator of MHC class I genes as well as genes involved in the MHC-I dependent antigen presentation pathway. Moreover, we discovered that NLRC5-mediated MHC class I transactivation pathway constitutes a major mechanism for immune evasion in multiple cancers and NLRC5 expression was significantly associated with activation of CD8 cytotoxic T cells and patient survival in melanoma and other cancers. In this proposal, we analyzed the effectiveness of NLRC5 as a prognostic and predictive biomarker in melanoma. We have analyzed the melanoma patient cohort who received anti-CTLA4 therapy or anti-PD1 therapy. Our data showed that the expression level is associated with the response to checkpoint blocking therapies. This study suggests that NLRC5 expression would be an useful biomarker to determine the appropriate therapy for the cancer patients.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、NLRC5の発現が免疫チェックポイント阻害剤の効果に必要であるかを検証するために、ヒト癌患者サンプルおよび動物モデルを用いて実験解析し、免疫チェックポイント阻害剤の効果を予測するための新たなバイオマーカーを開発することが目的であった。研究の結果、NLRC5の発現度およびDNAメチル化が癌患者生存予測のためのバイオマーカーとして有用であることが分かり、今後の癌患者治療において極めて重要な発見になったことが示された。