ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Colorectal Cancer Metastases in the Liver Establish Immunosuppressive Spatial Networking between Tumor-Associated SPP1+ Macrophages and Fibroblasts.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.
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Who cites it
156 citing papers in PubMed, 1 synthesis or guideline pooled it, 177 citations in OpenAlex.
- Pooled it
- The anti-CD33 antibody drug conjugate gemtuzumab ozogamicin depletes and functionally resets CD33+ myeloid-derived suppressor cells in patients with metastatic cancer: a phase 2 single-arm, open-label trial.Journal of leukocyte biology · 2026Trial
- Final results of ANICCA-Class II, a single arm, open-label phase II trial assessing nivolumab in tissue-specific class II expressing metastatic microsatellite stable colorectal cancer, with a parallel assessment of the immunoscore-immune checkpoint as a predictive biomarker for single-agent anti-PD-1.Journal for immunotherapy of cancer · 2025Trial
- SLC39-driven zinc influx orchestrates pleiotropic tumor-immune system cross-talk to establish immune suppression in colorectal cancer.Science advances · 2026Article
- Integrated spatial and single-cell transcriptomics uncover IFI6⁺ regulatory T-cells and SPP1⁺ macrophages immunosuppressive niches in colorectal cancer.British journal of cancer · 2026Article
- Review
- Review
- Single-Cell Transcriptomics and Mendelian Randomization Analysis Reveal Key Genes in Atrial Fibrillation.Journal of cardiovascular electrophysiology · 2026Article
- Review
- Evolution of SPP1Cell reports. Medicine · 2026Article
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
- Macrophage Plasticity in Cancer Therapy: Function, Timing, and Tradeoffs.International journal of molecular sciences · 2026Review
- Article
- APOC1⁺IFI30⁺ TAMs orchestrate colorectal cancer liver metastasis by coupling cholesterol biosynthesis with secretion of immunosuppressive factors.Cellular and molecular life sciences : CMLS · 2026Article
- A pan-cancer single-cell atlas uncovers the role of sex hormones and chromosomes in sex-divergent reprogramming of the tumor microenvironment.Cell communication and signaling : CCS · 2026Article
- EGFR deletion in myeloid cells reprograms the immunosuppressive landscape of colorectal cancer.Cell death and differentiation · 2026Article
- The Potential and Challenges of Focused Ultrasound-Mediated Therapies in the Management of Liver and Biliary Tract Cancers.Cancers · 2026Review
- Targeting USP14 enhances immunotherapy response by reprogramming tumor-associated macrophages in colon cancer.iScience · 2026Article
- Integrated Single-Cell and Bulk RNA Sequencing Identifies Macrophage Heterogeneity and Mitophagy-Related Biomarkers in Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2026Article
- Neuroactive ligand-receptor interaction in gastric cancer: a comprehensive spatial single-cell analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
96 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeThe liver is the most frequent metastatic site for colorectal cancer. Its microenvironment is modified to provide a niche that is conducive for colorectal cancer cell growth. This study focused on characterizing the cellular changes in the metastatic colorectal cancer (mCRC) liver tumor microenvironment (TME). EXPERIMENTAL
designWe analyzed a series of microsatellite stable (MSS) mCRCs to the liver, paired normal liver tissue, and peripheral blood mononuclear cells using single-cell RNA sequencing (scRNA-seq). We validated our findings using multiplexed spatial imaging and bulk gene expression with cell deconvolution.
resultsWe identified TME-specific SPP1-expressing macrophages with altered metabolism features, foam cell characteristics, and increased activity in extracellular matrix (ECM) organization. SPP1+ macrophages and fibroblasts expressed complementary ligand-receptor pairs with the potential to mutually influence their gene-expression programs. TME lacked dysfunctional CD8 T cells and contained regulatory T cells, indicative of immunosuppression. Spatial imaging validated these cell states in the TME. Moreover, TME macrophages and fibroblasts had close spatial proximity, which is a requirement for intercellular communication and networking. In an independent cohort of mCRCs in the liver, we confirmed the presence of SPP1+ macrophages and fibroblasts using gene-expression data. An increased proportion of TME fibroblasts was associated with the worst prognosis in these patients.
conclusionsWe demonstrated that mCRC in the liver is characterized by transcriptional alterations of macrophages in the TME. Intercellular networking between macrophages and fibroblasts supports colorectal cancer growth in the immunosuppressed metastatic niche in the liver. These features can be used to target immune-checkpoint-resistant MSS tumors.
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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.