ArticleJournal for immunotherapy of cancer2023
Geospatial characterization of immune cell distributions and dynamics across the microenvironment in clear cell renal cell carcinoma.
Article in Journal for immunotherapy of cancer, 2023. 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, 23 citations in OpenAlex.
- APOEScience advances · 2026Article
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- Spatial Clustering of Recently Activated Cytotoxic Lymphocytes Improves Association with Overall Survival in Women with High-Grade Serous Ovarian Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- Tumor-infiltrating B cells participate in shaping the immunosuppressive microenvironment in solid tumors.International journal of cancer · 2026Review
- Article
- Tumor-reactive TCRs within exhausted TILs reveal cancer type-specific immune landscapes in renal cell carcinoma.Frontiers in immunology · 2026Article
- Immunosuppressive cell populations as potential drivers of extrinsic immune checkpoint inhibition resistance in clear cell renal cell carcinoma.Oncology reviews · 2026Review
- Article
- Fibroblast Activation Protein Alpha (FAP) Expression Is Associated with Disease Recurrence and Poor Response to Tyrosine Kinase Inhibitors in Advanced Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2025Article
- Article
- Immunological features of clear-cell renal-cell carcinoma and resistance to immune checkpoint inhibitors.Nature reviews. Nephrology · 2025Review
- An in situ engineered chimeric IL-2 receptor potentiates the tumoricidal activity of proinflammatory CAR macrophages in renal cell carcinoma.Nature cancer · 2025Article
- Spatial expression of fibroblast activation protein-α in clear cell renal cell carcinomas revealed by multiplex immunoprofiling analysis of the tumor microenvironment.Cancer immunology, immunotherapy : CII · 2025Article
- Orchestration of Tumor-Associated Macrophages in the Tumor Cell-Macrophage-CD8International journal of biological sciences · 2025Review
- Increased spatial coupling of integrin and collagen IV in the immunoresistant clear-cell renal-cell carcinoma tumor microenvironment.Genome biology · 2024Article
- Analyzing the Spatial Distribution of Immune Cells in Lung Adenocarcinoma.Journal of personalized medicine · 2024Article
- Interferon signaling and ferroptosis in tumor immunology and therapy.NPJ precision oncology · 2024Article
- Integrated analysis of tertiary lymphoid structures and immune infiltration in ccRCC microenvironment revealed their clinical significances: a multicenter cohort study.Journal for immunotherapy of cancer · 2024Article
- Single-cell transcriptomic analysis in clear cell renal cell carcinoma: Deciphering the role of APP within the tumour microenvironment.Journal of cellular and molecular medicine · 2024Article
- Unveiling spatial complexity in solid tumor immune microenvironments through multiplexed imaging.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
introductionIn clear cell renal cell carcinoma (ccRCC), tumor-associated macrophage (TAM) induction of CD8+T cells into a terminally exhausted state has been implicated as a major mechanism of immunotherapy resistance, but a deeper biological understanding is necessary.
methodsPrimary ccRCC tumor samples were obtained from 97 patients between 2004 and 2018. Multiplex immunofluorescence using lymphoid and myeloid markers was performed in seven regions of interest per patient across three predefined zones, and geospatial analysis was performed using Ripley's K analysis, a methodology adapted from ecology.
resultsClustering of CD163+M2 like TAMs into the stromal compartment at the tumor-stroma interface was associated with worse clinical stage (tumor/CD163+nK(75): stage I/II: 4.4 (IQR -0.5 to 5.1); stage III: 1.4 (IQR -0.3 to 3.5); stage IV: 0.6 (IQR -2.1 to 2.1); p=0.04 between stage I/II and stage IV), and worse overall survival (OS) and cancer-specific survival (CSS) (tumor/CD163+nK(75): median OS-hi=149 months, lo=86 months, false-discovery rate (FDR)-adj. Cox p<0.001; median CSS-hi=174 months, lo=85 months; FDR-adj. Cox p<0.001). An RNA-seq differential gene expression score was developed using this geospatial metric, and was externally validated in multiple independent cohorts of patients with ccRCC including: TCGA KIRC, and the IMmotion151, IMmotion150, and JAVELIN Renal 101 clinical trials. In addition, this CD163+ geospatial pattern was found to be associated with a higher TIM-3+ proportion of CD8+T cells, indicative of terminal exhaustion (tumor-core: 0.07 (IQR 0.04-0.14) vs 0.40 (IQR 0.15-0.66), p=0.05).
conclusionsGeospatial clustering of CD163+M2 like TAMs into the stromal compartment at the tumor-stromal interface was associated with poor clinical outcomes and CD8+T cell terminal exhaustion.
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