AI-powered Immune Cell Knowledge Graph (ICKG) with granular immune contexts enables immune program interpretation

The widespread application of single-cell and spatial omics to models and patient samples has transformed immune cell profiling across physiological conditions. However, knowledge of immune cell states, functions, and gene regulation remains fragmented across publications, limiting our ability to synthesize insights and derive mechanistic understanding from the literature. To address this gap and facilitate literature integration, we constructed Immune Cell Knowledge Graphs (ICKGs)-four cell type-specific graphs derived from over 24,000 cancer immunotherapy-focused PubMed abstracts using large language models (LLMs) with "human verifiable" validation. Unlike conventional databases, which provide context-agnostic pathways, ICKGs capture directed, literature-supported relationships among genes, pathways and immune functions, enabling context-aware reasoning. We validated ICKGs using perturbation datasets from cytokine stimulation and CRISPR experiments, demonstrating that ICKGs contain more accurate and immunologically coherent contexts than canonical databases. As a key application, ICKGs provide interpretable and accurate pathway annotations, including signatures unannotated by canonical databases or used in immuno-oncology. To support community use, we created an interactive portal (https://kchen-lab.github.io/immune-knowledgegraph.github.io/) to perform ICKG-based pathway annotations, allowing researchers to explore immune cell-specific insights grounded in literature. This work establishes ICKGs as a scalable framework for immune-specific functional interpretation and mechanistic hypothesis generation in single-cell and spatial omics.