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Cancer immunology data engine reveals secreted AOAH as a potential immunotherapy

Lanqi Gong1, Jie Luo2, Emily Yang1

  • 1Cancer Data Science Lab, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

Cell
|July 29, 2025
PubMed

Insights

A new tool, the Cancer Immunology Data Engine (CIDE), identifies novel secreted proteins like AOAH that enhance cancer immunotherapy by improving T cell responses and protecting dendritic cells.

Area of Science:

  • Immunology
  • Genomics
  • Oncology

Background:

  • Secreted proteins mediate intercellular communication and are potential therapeutic targets.
  • Studying the ~1,903 human secreted protein genes is challenging with traditional genetic methods.
  • Discovering novel cancer therapeutics is a critical unmet need.

Purpose of the Study:

  • To develop a comprehensive data engine for studying secreted proteins in cancer.
  • To identify novel secreted protein targets that can enhance cancer immunotherapy outcomes.
  • To validate the role of specific secreted proteins in modulating anti-tumor immunity.

Main Methods:

  • Developed the Cancer Immunology Data Engine (CIDE) integrating 90 omics datasets from 8,575 tumor profiles across 17 solid tumor types.
  • Systematically identified genes associated with immunotherapy outcomes using CIDE.
  • Prioritized secreted proteins with no known cancer roles and validated their function in mouse models.

Main Results:

  • CIDE successfully identified genes linked to immunotherapy response.
  • Validated four secreted proteins (AOAH, CR1L, COLQ, ADAMTS7) with regulatory effects on immune checkpoint blockade.
  • Acyloxyacyl hydrolase (AOAH) emerged as a top hit, potentiating immunotherapy by enhancing T cell receptor sensitivity and protecting dendritic cells.

Conclusions:

  • The Cancer Immunology Data Engine (CIDE) is a valuable resource for discovering secreted protein targets in cancer immunotherapy.
  • AOAH enhances anti-tumor immunity and represents a promising therapeutic target for improving immunotherapy efficacy.
  • Targeting specific secreted proteins can overcome resistance mechanisms and improve patient outcomes in cancer treatment.
Keywords:
ADAMTS7AOAHCOLQCR1Lacyloxyacyl hydrolasearachidonoyl phosphatidylcholinecancer immunotherapydatabaseoxidized phospholipidsecreted protein

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