ArticleThe Journal of experimental medicine2025
Tumor cell heterogeneity drives spatial organization of the intratumoral immune response.
Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- UBE2A as a prognostic indicator across human cancers: Insights from multi‑omics and immune landscape analyses.Molecular medicine reports · 2026Article
- Pan-tumor spatial transcriptomics reveals conserved properties of tumor organization.Cell reports. Medicine · 2026Article
- Spatially organized regulated cell death-immune coupling in solid tumors: integrating spatial omics with actionable regulated cell death biology.Molecular cancer · 2026Review
- Bacterial-based cancer therapy: mechanisms and therapeutic advances.Molecular biomedicine · 2026Review
- CIT tumor lines: A series of immunogenic murine cutaneous squamous cell carcinoma cell lines derived from chemical carcinogenesis.JID innovations : skin science from molecules to population health · 2026Article
- Cancer Heterogeneity and Cancer Cell Plasticity: Molecular Mechanisms and Precision Therapy.MedComm · 2026Review
- Spatial Heterogeneity of Intratumoral Microbiota and Its Roles in Tumor-Microbiota Interactions and Therapeutic Implications.Pathogens (Basel, Switzerland) · 2026Review
- Spatial architecture of the melanoma immune niche reveals CORO1A as a functional hub for T cell cytotoxicity and immunotherapy synergy.Journal of translational medicine · 2026Article
- Review
- Single-cell TCR mapping reveals spatially coordinated T cell states in head and neck cancer.Science immunology · 2026Article
- SLC2A1Nature cell biology · 2026Article
- Immunosuppressive tumor microenvironment and immunotherapy resistance of esophageal carcinoma.Frontiers in immunology · 2026Review
- Predictive and mechanistic insights ofPeerJ · 2026Article
- Quantitative profiling of intratumor immune heterogeneity identifies loss of immune diversity as a hallmark of cancer progression.NPJ precision oncology · 2025Article
- The applications of single-cell multiomics in drug screening.Pharmaceutical science advances · 2025Review
- Cold, Hot, and Lethal-The Tumour Microenvironment and the Immunology of Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2025Review
- Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.Signal transduction and targeted therapy · 2025Review
- Orthotopically Implanted Murine Lung Adenocarcinoma Cell Lines for Preclinical Investigations.Cancers · 2025Review
- Masters of adaptation: How cancer and immune cell plasticity mediates tumor progression.PLoS biology · 2025Review
- Exo-nanomaterials in cancer immunotherapy: reprogramming the tumor immune microenvironment.Frontiers in immunology · 2025Review
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18 authors.
Funding
Abstract
Intratumoral heterogeneity (ITH)-defined as genetic and cellular diversity within a tumor-is linked to failure of immunotherapy and an inferior anti-tumor immune response. We modeled heterogeneous tumors comprised of "hot" and "cold" tumor populations (giving rise to T cell-rich and T cell-poor tumors, respectively) and introduced fluorescent labels to enable precise spatial tracking. We found the cold tumor cell population exerted a "dominant cold" effect in mixed tumors. Strikingly, spatial analysis revealed that the tumor cells themselves created distinct local microenvironments within heterogeneous tumors: regions occupied by cold tumor cells showed pronounced immunosuppression, harboring increased CD206Hi macrophages and diminished local T cell function. This inferior T cell activity in cold regions persisted even after immunotherapy and mechanistically was mediated by CX3CL1 produced by the cold tumor cells. An immune cold tumor population within a heterogeneous tumor thus impairs tumor immunity on both a tumor-wide and a highly localized spatial scale.
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