ArticleJournal for immunotherapy of cancer2025
Spatial transcriptomic profiling of metastatic renal cell carcinoma identifies chemokine-driven macrophage and CD8+ T-cell interactions predictive of immunotherapy response.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- A renal cyst-clear cell renal cell carcinoma comorbidity analysis identifies a FOXM1-positive epithelial COL6A1-CD44 axis that remodels fibroblasts.Translational oncology · 2026Article
- Biomarkers in Clear Cell Renal Cell Carcinoma: From Biological Association to Clinical Decision-Making.Genes · 2026Review
- Spatial and Temporal Heterogeneity of Macrophage Efferocytosis in Tumors: Emerging Implications for Immunotherapy Biomarkers and Therapeutic Timing.Cancer medicine · 2026Review
- Review
- Review
- Organ-Specific Migration License (OSML) theory: a novel paradigm for spatiotemporal regulation and intervention of cross-organ immune cell migration in tumor immune responses.Cell communication and signaling : CCS · 2026Review
- Spatial transcriptomic profiling of metastatic renal cell carcinoma identifies chemokine-driven macrophage and CD8+ T-cell interactions predictive of immunotherapy response.Journal for immunotherapy of cancer · 2025Article
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9 authors.
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Abstract
backgroundMetastatic renal cell carcinoma (mRCC) still lacks tissue-based biomarkers that predict benefit from first-line immune checkpoint inhibitor (ICI) regimens. High-resolution spatial transcriptomics can dissect the tumor microenvironment (TME) and reveal prognostic niches invisible to bulk assays, offering a path toward precision immunotherapy.
methodsFormalin-fixed, paraffin-embedded samples from 12 therapy-naïve patients with mRCC treated with ICI-based combinations were profiled with 10x Genomics Visium and NanoString COSMx. Six patients contributed matched metastatic lesions. Cell-type deconvolution used robust cell type decomposition with a public single-cell RNA-seq reference. Clinical outcomes (mean follow-up 16.75 months) were correlated with spatial features. Validation employed Phase 2/3 JAVELIN Renal 101 as well as Checkmate 010/025 transcriptomic data.
resultsSpatial transcriptomics uncovered pronounced divergences between primary tumors and metastases in cellular composition and microarchitectural organization. Canonical RCC molecular subtypes displayed marked intrapatient and interpatient spatial heterogeneity, underscoring limitations of bulk classifications. Five recurrent immune niches emerged across samples. One niche-rich in macrophages and CD8
conclusionMetastasis-specific immune niches, rather than primary-tumor characteristics, appear decisive for ICI efficacy in mRCC. Spatial transcriptomic profiling can identify these clinically relevant microenvironments and generate transferable gene signatures, supporting biomarker-driven patient selection and trial design. Integrating spatial TME analysis into future studies may accelerate personalized immunotherapy strategies for mRCC.
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