ArticleNature communications2025
Lymph nodes molecular subtypes unravel lymph nodes heterogeneity and clinical implications in colorectal cancer.
Article in Nature communications, 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- Tumor-Regional Immune Microenvironment: A Critical Factor in the Design of Radiotherapy-Immunotherapy Combination Trials.International journal of cancer · 2026Review
- Establishment and characterization of mouse lymph node fibrosis models.Animal models and experimental medicine · 2026Article
- CXCL1 as a novel prognostic biomarker and immune regulator in colon adenocarcinoma.Discover oncology · 2026Article
- Single-cell omics in tumor lymph node metastasis: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Tumor tissue-associatedFrontiers in cellular and infection microbiology · 2026Article
- Understanding the immune microenvironment of ovarian cancer.Frontiers in oncology · 2026Review
- The evolving role of the immune microenvironment of tumor draining lymph nodes in the development of biomarkers of non-small cell lung cancer.Frontiers in oncology · 2026Review
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Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lymph nodes (LNs) play a pivotal role in colorectal cancer (CRC) progression and immunity, yet their molecular and functional diversity remains poorly understood. By analyzing 630 LNs and 88 primary tumors from 200 CRC patients across four independent cohorts using bulk and single-cell RNA sequencing, we identify four non-metastatic negative LNs (NLN) subtypes (NLN_C1-C4) exhibiting obviously different immune function and stromal expansion. NLN_C3/C4 are characterized by diminished T and B cell activity and fibroblast-driven fibrosis, with follicular dendritic cell loss contributing to B cell dysfunction. Immune checkpoint inhibitors partially reverse these effects, restoring FDC and B cell activity. LNs subtypes demonstrate heterogeneity across patients and within individuals, with higher NLN_C3/C4 proportions associated with advanced tumor stages, poorer survival, and recurrence. Here, we report LNs subtypes as critical manifestations of LN heterogeneity in CRC, providing a basis for improved clinical stratification and LN-targeted therapeutic strategies.
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Registered trials
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