A clinical oncology research team at the LKS Faculty of Medicine, the University of Hong Kong (HKUMed), in collaboration with the US National Cancer Institute (NCI), has developed an innovative big data platform, called the “Cancer Immunology Data Engine” (CIDE). This state-of-the-art platform integrates clinical outcomes from 5,957 cancer patients worldwide who received immunotherapy, along with comprehensive multi-omics datasets covering 17 cancer types and comprising 8,575 tumor samples.
CIDE represents the most extensive database for tumor immunotherapy available to date. Currently publicly accessible via the NCI website, the platform enables researchers worldwide to explore and analyze clinical trial data in depth, thereby accelerating advances in cancer immunotherapy research.
Professor Guan Xinyuan, Sophie Y M Chan, Professor of Cancer Research and Chair Professor of the Department of Clinical Oncology, Center of Cancer Medicine, School of Clinical Medicine, HKUMed, together with Dr. Jiang Peng of the NCI, highlighted, “The human genome contains approximately 1,903 genes encoding secreted proteins, 61% of which remain functionally uncharacterized in cancer development.
“By applying CIDE, our team conducted a comprehensive analysis and identified genes strongly associated with pan-cancer immunotherapy outcomes, including multiple secreted proteins whose relevance to cancer had not previously been recognized.
“Among these, acyloxyacyl hydrolase (AOAH) emerged as the most prominent candidate, demonstrating significant immunotherapeutic potential across diverse tumor types, such as melanoma, pancreatic cancer, hepatocellular carcinoma, colorectal cancer, and kidney cancer.”
The research was published in the journal Cell.
How AOAH activates the immune system to target cancer cells
The study systematically uncovered a unique molecular mechanism by which AOAH enhances anti-tumor immunity. AOAH, a secreted lipase, eliminates specific phosphatidylcholine molecules that suppress immune responses within the tumor microenvironment. This action helps restore and strengthen the immune system’s ability to fight cancer, particularly by boosting CD8+ T-cell activation and tumor killing capacity, while also helping dendritic cells regain their ability to present antigens and initiate immune responses.
Notably, most advanced tumors evade immune surveillance by reducing their antigen visibility and immunogenicity, posing a major challenge for immunotherapy in patients with advanced cancers. By directly addressing this issue, AOAH is positioned as a critical modulator to overcome immune escape in advanced cancers.
AOAH potentiates multiple cancer immunotherapies
In murine models of melanoma, hepatocellular carcinoma and kidney cancer, AOAH significantly prolonged mouse survival when combined with immune checkpoint inhibitors or TCR-T cell therapy.
Intratumoral injection of AOAH protein also produced robust immune activation and demonstrated synergistic benefits when combined with anti-PD-1 and anti-CTLA-4 treatments, underscoring its capacity to augment multiple therapeutic regimens. Mechanistically, AOAH promotes infiltration of key immune cells into the tumor microenvironment, particularly CD8+ T cells and CD11+ dendritic cells.
These cells are essential for antigen recognition, immune signal transmission and immune activation, which are critical to the success of immunotherapy. AOAH demonstrates standalone therapeutic potential and acts as a powerful complement to existing immunotherapies, offering a promising strategy for overcoming immune resistance in advanced cancers.
AOAH as a novel anticancer modality in combination therapy
Secreted proteins play a pivotal role in cell-cell communication and immune modulation. Their diffusive effects enable coordinated immune responses across the tumor microenvironment, lymph nodes, and immune organs.
Building on this principle, the research team is designing antibody-drug conjugates that combine AOAH with PD-L1 antibodies, offering a next-generation precision immunotherapy capable of targeting both tumor cells and their microenvironment.
Pre-clinical studies in mouse models will evaluate the efficacy, safety, and modes of action of this approach.
Professor Guan remarked, “We are currently advancing early-phase clinical trials and aim to improve the cure rate for patients with refractory, advanced cancers from the current 5–20% to over 40%. Leveraging the strategic advantages of the Guangdong–Hong Kong–Macao Greater Bay Area, we aim to translate this innovation globally to benefit cancer patients worldwide.”
More information:
Lanqi Gong et al, Cancer immunology data engine reveals secreted AOAH as a potential immunotherapy, Cell (2025). DOI: 10.1016/j.cell.2025.07.004
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