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. 2025 Sep 4;188(18):5062-5080.e32.
doi: 10.1016/j.cell.2025.07.004. Epub 2025 Jul 28.

Cancer immunology data engine reveals secreted AOAH as a potential immunotherapy

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

Cancer immunology data engine reveals secreted AOAH as a potential immunotherapy

Lanqi Gong et al. Cell. .

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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Conflict of interest statement

Declaration of interests NCI has filed a provisional patent based on this work, with P.J. and L.G. as inventors.

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