ArticleCancer research communications2023
Peritumoral Immune-suppressive Mechanisms Impede Intratumoral Lymphocyte Infiltration into Colorectal Cancer Liver versus Lung Metastases.
Article in Cancer research communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 10 citations in OpenAlex.
- Review
- Overall survival of immunotherapy versus standard of care in chemorefractory microsatellite stable metastatic colorectal cancer: a propensity score matched analysis of 708 patients.Journal for immunotherapy of cancer · 2026Article
- Revised tumor burden score for prognostic stratification in metastatic colorectal cancer patients receiving immunotherapy: a retrospective study.The oncologist · 2026Observational
- Baseline Tumor Features and Systemic Immune Dynamics Underlying Efficacy in MSS Metastatic Colorectal Cancer Treated with Regorafenib, Ipilimumab, and Nivolumab.Cancer immunology research · 2026Article
- Organ-specific pre-metastatic and metastatic niches in colorectal cancer: "discrepancy in response to immune checkpoint inhibitors in liver and lung metastasis".Frontiers in immunology · 2026Review
- Macrophages in Colorectal Cancer: from Normal Mucosa to Distant Metastasis: Beyond the M1/M2 Paradigm.Journal of Cancer · 2026Review
- Beyond mismatch repair in colorectal cancer liver metastases: rethinking immunotherapy through the hepatic metastatic niche.Frontiers in immunology · 2026Article
- Tumor Immune Microenvironment and Current Status of Immune Checkpoint Inhibitor Therapy in Colorectal Cancer Liver Metastasis.Current oncology (Toronto, Ont.) · 2025Review
- Computed tomography-dominant surveillance strategies for colorectal cancer: Improving early detection of recurrence.World journal of gastrointestinal surgery · 2025Article
- Liver metastases and peritoneal metastases and response to checkpoint inhibitors in metastatic colorectal cancer with microsatellite instability.The oncologist · 2024Article
- Organ-Specific Immune Setpoints Underlie Divergent Immune Profiles across Metastatic Sites in Breast Cancer.Cancer immunology research · 2024Article
- Complete response of metastatic microsatellite-stableOncoimmunology · 2024Article
- Neuroimmune cell interactions and chronic infections in oral cancers.Frontiers in medicine · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Patients with microsatellite stable (MSS) colorectal cancer with liver metastases are resistant to immune checkpoint inhibitor (ICI) therapy, while about one-third of patients with colorectal cancer without liver metastases, particularly those with lung-only metastases, respond to ICI. We analyzed primary colorectal cancer tumors and major metastatic sites (liver, lung, peritoneal) using multiplex immunofluorescence and whole-slide spatial analyses to identify variations in immune contexture and regional localization within the tumor microenvironment. While levels of T and B cells within peritumoral regions were similar, their levels were significantly lower within the tumor core of liver and peritoneal metastases compared with lung metastases. In contrast, antigen-presenting cells (APC) and APC-T cell interactions were more abundant in all regions of lung metastases. We also identified an abundance of lymphoid aggregates throughout lung metastases, but these were present only within peritumoral regions of liver and peritoneal metastases. Larger lymphoid aggregates consistent with features of tertiary lymphoid structures were observed within or adjacent to primary tumors, but not metastatic lesions. Our findings were validated using NanoString GeoMx DSP, which further showed that liver metastases had higher expression of immune-suppressive markers, while lung metastases showed higher proinflammatory activity and T-cell activation markers. Peritoneal metastases demonstrated higher expression of cancer-associated fibroblast-related proteins and upregulated PD-1/PD-L1 signaling molecules. Our results demonstrate that functional status and spatial distribution of immune cells vary significantly across different metastatic sites. These findings suggest that metastatic site-dependent immune contexture may underlie discordant responses to ICI therapy in patients with MSS colorectal cancer. SIGNIFICANCE: Our results demonstrate that functional status and spatial distribution of immune cells vary significantly across different metastatic sites in MSS colorectal cancer. These findings suggest that metastatic site-dependent immune contexture may underlie discordant responses to ICI therapy in patients with MSS colorectal cancer.
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