2. Academic Validation
  3. A method for predicting drugs that can boost the efficacy of immune checkpoint blockade

A method for predicting drugs that can boost the efficacy of immune checkpoint blockade

  • Nat Immunol. 2024 Mar 18. doi: 10.1038/s41590-024-01789-x.
Yun Xia # 1 2,  Xin Li # 3,  Nana Bie 3,  Wen Pan 2,  Ya-Ru Miao 2,  Mei Yang 2,  Yan Gao 2,  Chuang Chen 4,  Hanqing Liu 4,  Lu Gan 5,  An-Yuan Guo 6 7
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China.
  • 2 Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
  • 3 National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Department of Breast and Thyroid Surgery, Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.
  • 5 National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China. lugan@mail.hust.edu.cn.
  • 6 Department of Thoracic Surgery, West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China. guoanyuan@wchscu.cn.
  • 7 Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China. guoanyuan@wchscu.cn.
  • # Contributed equally.
PMID: 38499799 DOI: 10.1038/s41590-024-01789-x
Abstract

Combination therapy is a promising therapeutic strategy to enhance the efficacy of immune checkpoint blockade (ICB); however, predicting drugs for effective combination is challenging. Here we developed a general data-driven method called CM-Drug for screening compounds that can boost ICB treatment efficacy based on core and minor gene sets identified between responsive and nonresponsive samples in ICB therapy. The CM-Drug method was validated using melanoma and lung Cancer mouse models, with combined therapeutic efficacy demonstrated in eight of nine predicted compounds. Among these compounds, taltirelin had the strongest synergistic effect. Mechanistic analysis and experimental verification demonstrated that taltirelin can stimulate CD8+ T cells and is mediated by the induction of thyroid-stimulating hormone. This study provides an effective and general method for predicting and evaluating drugs for combination therapy and identifies candidate compounds for future ICB combination therapy.

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