ArticleProceedings of the National Academy of Sciences of the United States of America2023
The spread of interferon-γ in melanomas is highly spatially confined, driving nongenetic variability in tumor cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 27 citations in OpenAlex.
- Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: a phase 2 trial with biomarker analyses.Nature medicine · 2024Trial
- The effects of IFNγ on tissue physiology through structural cells.Nature reviews. Immunology · 2026Review
- Mechanistic trade-offs between local and long-range signaling activity in natural and synthetic morphogens.Science advances · 2026Article
- Article
- NOS2 and COX2 impact the spatial landscape of CD8Redox biology · 2026Review
- Immune Evasion in Prostate Cancer: Resolving the Cold Tumour Paradox via a Hybrid Discrete-Continuum Computational Framework.Biology · 2026Article
- A Hallmark-Integrated, Agent-Based Framework for Intratumor Heterogeneity in Melanoma Evolution.Bulletin of mathematical biology · 2026Article
- Spatial instruction of tissue immunity.ImmunoHorizons · 2026Review
- IFNγ-induced memory in human macrophages is sustained by the durability of cytokine signaling itself.The Journal of experimental medicine · 2026Article
- Spatio-temporal modelling of in vitro influenza A virus infection: The impact of defective interfering particles on the type I interferon response.PLoS computational biology · 2026Article
- ICAM-1 identifies preadipocytes and restricts white adipogenesis by adhering immune cells.Cell death and differentiation · 2026Article
- Spatial microenvironments tune immune response dynamics in the Drosophila larval fat body.PLoS genetics · 2026Article
- Deciphering immunosuppressive niches by spatial single-cell proteomics: spatial interaction networks and translational opportunities.Frontiers in immunology · 2026Review
- Spatio-temporal modelling ofbioRxiv : the preprint server for biology · 2025Article
- Spatial microenvironments tune immune response dynamics in thebioRxiv : the preprint server for biology · 2025Article
- Macrophage-T Cell Physical Interaction Modulates IFN-γ Secretion.ACS applied materials & interfaces · 2025Article
- Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant.Cell reports · 2025Article
- IFNγ-induced memory in human macrophages is not sustained by epigenetic changes but the durability of the cytokine itself.bioRxiv : the preprint server for biology · 2025Article
- Masters of adaptation: How cancer and immune cell plasticity mediates tumor progression.PLoS biology · 2025Review
- Dual role of interferon-gamma in the response of melanoma patients to immunotherapy with immune checkpoint inhibitors.Molecular cancer · 2025Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interferon-γ (IFNγ) is a critical antitumor cytokine that has varied effects on different cell types. The global effect of IFNγ in the tumor depends on which cells it acts upon and the spatial extent of its spread. Reported measurements of IFNγ spread vary dramatically in different contexts, ranging from nearest-neighbor signaling to perfusion throughout the entire tumor. Here, we apply theoretical considerations to experiments both in vitro and in vivo to study the spread of IFNγ in melanomas. We observe spatially confined niches of IFNγ signaling in 3-D mouse melanoma cultures and human tumors that generate cellular heterogeneity in gene expression and alter the susceptibility of affected cells to T cell killing. Widespread IFNγ signaling only occurs when niches overlap due to high local densities of IFNγ-producing T cells. We measured length scales of ~30 to 40 μm for IFNγ spread in B16 mouse melanoma cultures and human primary cutaneous melanoma. Our results are consistent with IFNγ spread being governed by a simple diffusion-consumption model and offer insight into how the spatial organization of T cells contributes to intratumor heterogeneity in inflammatory signaling, gene expression, and immune-mediated clearance. Solid tumors are often viewed as collections of diverse cellular "neighborhoods": Our work provides a general explanation for such nongenetic cellular variability due to confinement in the spread of immune mediators.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.