2. Academic Validation
  3. Cancer immunology data engine reveals secreted AOAH as a potential immunotherapy

Cancer immunology data engine reveals secreted AOAH as a potential immunotherapy

  • Cell. 2025 Sep 4;188(18):5062-5080.e32. doi: 10.1016/j.cell.2025.07.004.
Lanqi Gong 1,  Jie Luo 2,  Emily Yang 1,  Beibei Ru 1,  Ziyang Qi 2,  Yuma Yang 2,  Anshu Rani 1,  Abhilasha Purohit 1,  Yu Zhang 3,  Grace Guan 1,  Rohit Paul 4,  Trang Vu 1,  Zuojia Chen 5,  Renyue Ji 6,  Chi-Ping Day 1,  Chuan Wu 5,  Glenn Merlino 7,  David Fitzgerald 8,  Grégoire Altan-Bonnet 9,  Kenneth Aldape 10,  Jiansheng Wu 11,  Xinyuan Guan 12,  Peng Jiang 13
Affiliations

Affiliations

  • 1 Cancer Data Science Lab, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
  • 2 Department of Clinical Oncology, The University of Hong Kong (HKU), Hong Kong, China.
  • 3 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Pediatric Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
  • 4 Office of the Director, CCR, NCI, NIH, Bethesda, MD 20892, USA.
  • 5 Experimental Immunology Branch, CCR, NCI, NIH, Bethesda, MD 20892, USA.
  • 6 School of Public Health, HKU, Hong Kong, China.
  • 7 Laboratory of Cancer Biology and Genetics, CCR, NCI, NIH, Bethesda, MD 20892, USA.
  • 8 Laboratory of Molecular Biology, CCR, NCI, NIH, Bethesda, MD 20892, USA.
  • 9 Laboratory of Integrative Cancer Immunology, CCR, NCI, NIH, Bethesda, MD 20892, USA.
  • 10 Laboratory of Pathology, CCR, NCI, NIH, Bethesda, MD 20892, USA.
  • 11 WuXi Biologics, 7 Clark Drive, Cranbury, NJ 08512, USA.
  • 12 Department of Clinical Oncology, The University of Hong Kong (HKU), Hong Kong, China. Electronic address: xyguan@hku.hk.
  • 13 Cancer Data Science Lab, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Electronic address: peng.jiang@nih.gov.
PMID: 40730154 DOI: 10.1016/j.cell.2025.07.004
Abstract

Secreted proteins are central mediators of intercellular communications and can serve as therapeutic targets in diverse diseases. The ∼1,903 human genes encoding secreted proteins are difficult to study through common genetic approaches. To address this hurdle and, more generally, to discover Cancer therapeutics, we developed the Cancer Immunology Data Engine (CIDE, https://cide.CCR.Cancer.gov), which incorporates 90 omics datasets spanning 8,575 tumor profiles with immunotherapy outcomes from 17 solid tumor types. CIDE systematically identifies all genes associated with immunotherapy outcomes. Then, we focused on secreted proteins prioritized by CIDE without known Cancer roles and validated regulatory effects on immune checkpoint blockade for AOAH, CR1L, COLQ, and ADAMTS7 in mouse models. The top hit, acyloxyacyl hydrolase (AOAH), potentiates immunotherapies in multiple tumor models by sensitizing T cell receptors to weak antigens and protecting dendritic cells through depleting immunosuppressive arachidonoyl phosphatidylcholines and oxidized derivatives.

Keywords

ADAMTS7; AOAH; COLQ; CR1L; acyloxyacyl hydrolase; arachidonoyl phosphatidylcholine; cancer immunotherapy; database; oxidized phospholipid; secreted protein.

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