ArticleFrontiers in immunology2022
Multi-Scale Spatial Analysis of the Tumor Microenvironment Reveals Features of Cabozantinib and Nivolumab Efficacy in Hepatocellular Carcinoma.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 87 citations in OpenAlex.
- Virtual clinical trials of anti-PD-1 and anti-CTLA-4 immunotherapy in advanced hepatocellular carcinoma using a quantitative systems pharmacology model.Journal for immunotherapy of cancer · 2022Trial
- Cancer-associated fibroblasts in therapeutic resistance of hepatocellular carcinoma: evidence, mechanisms, and translational implications.Medical oncology (Northwood, London, England) · 2026Review
- Unraveling the tapestry: Lessons from multi-omics and spatial biology in hepatocellular cancer.Hepatology (Baltimore, Md.) · 2026Review
- The spatial architecture of tumor immunity: Emerging predictive biomarkers across cancer.Immunologic research · 2026Review
- Neoadjuvant Endocrine Treatment plus Mammaglobin-A DNA Vaccine Induces Antitumor Immune Responses in the Primary Tumor and Peripheral Blood of Patients with Breast Cancer: Insights from a Phase Ib Clinical Trial.Cancer immunology research · 2026Article
- Spatial proteomics in precision medicine: technologies, bioinformatics, and translational applications.Precision clinical medicine · 2026Review
- Robust analysis of the tumor spectrum in a preclinical model of breast cancer reveals stable subtypes with distinct growth patterns.Computer methods and programs in biomedicine · 2026Article
- Quantitative Calibration of a Spatial QSP Model Identifies Fibroblast Impact on HCC Immunotherapy.bioRxiv : the preprint server for biology · 2025Article
- PD-L1(+) tumor-associated macrophages induce CD8(+) T Cell exhaustion in hepatocellular carcinoma.Neoplasia (New York, N.Y.) · 2025Article
- [Prediction of Spatial Distance of CAFs-TAECs for Pathological Response to Neoadjuvant Chemoimmunotherapy in Lung Squamous Cell Carcinoma].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Article
- Bi-level graph learning unveils prognosis-relevant tumor microenvironment patterns in breast multiplexed digital pathology.Patterns (New York, N.Y.) · 2025Article
- Spatial Architecture of Single-Cell and Vasculature in Tumor Microenvironment Predicts Clinical Outcomes in Triple-Negative Breast Cancer.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025Article
- Pan-cancer convergence of tumour-immune microenvironment motifs revealed by CyTOF and imaging mass cytometry.Frontiers in immunology · 2025Review
- From surfing to diving into the tumor microenvironment through multiparametric imaging mass cytometry.Frontiers in immunology · 2025Review
- Letter to the Editor: Spatial proximity of tumor-immune interactions predicts patient outcome in hepatocellular carcinoma.Discover oncology · 2024Article
- Identification of the CD8Translational cancer research · 2024Article
- The prognostic effect of infiltrating immune cells is shaped by proximal M2 macrophages in lung adenocarcinoma.Molecular cancer · 2024Article
- Integration of Clinical Trial Spatial Multiomics Analysis and Virtual Clinical Trials Enables Immunotherapy Response Prediction and Biomarker Discovery.Cancer research · 2024Article
- Computational methods and biomarker discovery strategies for spatial proteomics: a review in immuno-oncology.Briefings in bioinformatics · 2024Review
- Omics-based molecular classifications empowering in precision oncology.Cellular oncology (Dordrecht, Netherlands) · 2024Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Background: Concomitant inhibition of vascular endothelial growth factor (VEGF) and programmed cell death protein 1 (PD-1) or its ligand PD-L1 is a standard of care for patients with advanced hepatocellular carcinoma (HCC), but only a minority of patients respond, and responses are usually transient. Understanding the effects of therapies on the tumor microenvironment (TME) can provide insights into mechanisms of therapeutic resistance. Methods: 14 patients with HCC were treated with the combination of cabozantinib and nivolumab through the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. Among them, 12 patients (5 responders + 7 non-responders) underwent successful margin negative resection and are subjects to tissue microarray (TMA) construction containing 37 representative tumor region cores. Using the TMAs, we performed imaging mass cytometry (IMC) with a panel of 27-cell lineage and functional markers. All multiplexed images were then segmented to generate a single-cell dataset that enables (1) tumor-immune compartment analysis and (2) cell community analysis based on graph-embedding methodology. Results from these hierarchies are merged into response-associated biological process patterns. Results: Image processing on 37 multiplexed-images discriminated 59,453 cells and was then clustered into 17 cell types. Compartment analysis showed that at immune-tumor boundaries from NR, PD-L1 level on tumor cells is significantly higher than remote regions; however, Granzyme B expression shows the opposite pattern. We also identify that the close proximity of CD8 Conclusion: These results demonstrate the feasibility of a novel application of multiplexed image analysis that is broadly applicable to quantitative analysis of pathology specimens in immuno-oncology and provides further evidence that CD163
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Registered trials
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.