Recently, researchers have successfully developed an innovative big data platform called the "Cancer Immunology Data Engine (CIDE)." This platform integrates clinical outcomes from 5,957 cancer patients worldwide who received immunotherapy, covering a comprehensive multi-omics dataset of 17 cancer types and containing 8,575 tumor samples. The study has been published in the journal Cell.
CIDE is the most comprehensive tumor immunotherapy database to date. The platform is now available to global researchers through the NCI website, supporting in-depth exploration and analysis of clinical trial data to accelerate progress in cancer immunotherapy research.
Figure 1. CIDE integrates 8,575 omics profiles from 5,957 patients with immunotherapy outcomes. (Gong L, et al., 2025)
The human genome contains approximately 1,903 genes encoding secretory proteins, 61% of which have unclear functions in cancer development. By applying CIDE, the research team conducted a comprehensive analysis and identified genes closely associated with pan-cancer immunotherapy outcomes, including several secretory proteins previously unrecognized as cancer-related. Among these, acyloxyacyl hydrolase (AOAH) emerged as the most prominent candidate factor, demonstrating significant immunotherapy potential across multiple tumor types, including melanoma, pancreatic cancer, hepatocellular carcinoma, colorectal cancer, and renal cell carcinoma.
How Does AOAH Activate the Immune System to Target Cancer Cells?
The study systematically revealed the unique molecular mechanism by which AOAH enhances anti-tumor immunity. This secretory lipase can clear specific phosphatidylcholine molecules in the tumor microenvironment that suppress immune responses. This action helps restore and strengthen the immune system's ability to combat cancer, particularly by enhancing the activation and tumor-killing capacity of CD8+ T cells while aiding dendritic cells in restoring their antigen presentation and immune response initiation capabilities.
Notably, most advanced tumors evade immune surveillance by reducing their antigen visibility and immunogenicity, posing a significant challenge to immunotherapy for late-stage cancer patients. AOAH directly addresses this issue, becoming a key regulatory factor in overcoming immune evasion in advanced cancers.
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CSC-DC000706 |
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CSC-SC000706 |
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AD01117Z |
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LV05119L |
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LV05120L |
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LV05121L |
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CDCH015866 |
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CDCR028354 |
AOAH Enhances Multiple Cancer Immunotherapies
In mouse models of melanoma, hepatocellular carcinoma, and renal cell carcinoma, AOAH combined with immune checkpoint inhibitors or TCR-T cell therapy significantly extended survival. Intratumoral injection of AOAH protein also produced robust immune activation effects and demonstrated synergistic benefits when used alongside anti-PD-1 and anti-CTLA-4 treatments, highlighting its ability to enhance various therapeutic regimens. Mechanistically, AOAH promoted the infiltration of critical immune cells-particularly CD8+ T cells and CD11+ dendritic cells-into the tumor microenvironment. These cells are essential for antigen recognition, immune signaling, and immune activation, processes critical to the success of immunotherapy. AOAH not only exhibits independent therapeutic potential but also serves as a powerful complement to existing immunotherapies, offering a promising strategy to overcome immune resistance in advanced cancers.
AOAH as a Novel Anti-Cancer Modality in Combination Therapy
Secretory proteins play a pivotal role in intercellular communication and immune regulation. Their diffusion effects can coordinate immune responses across the tumor microenvironment, lymph nodes, and immune organs. Based on this principle, the research team is designing antibody-drug conjugates that combine AOAH with PD-L1 antibodies, providing next-generation precision immunotherapy capable of simultaneously targeting tumor cells and their microenvironment. Preclinical studies in mouse models will evaluate the efficacy, safety, and mode of action of this approach.
Professor Guan stated, "We are currently advancing early clinical trials with the goal of increasing the cure rate for patients with refractory advanced cancer from the current 5-20% to over 40%."
Reference
Gong L, et al. Cancer immunology data engine reveals secreted AOAH as a potential immunotherapy. Cell, 2025, 188(18): 5062-5080. e32.