ArticleCancers2020
The Immune Phenotype of Isolated Lymphoid Structures in Non-Tumorous Colon Mucosa Encrypts the Information on Pathobiology of Metastatic Colorectal Cancer.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The trial behind it
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
10 citing papers in PubMed.
- The rules of different B cell subtypes in colorectal cancer: friends or foes?Future oncology (London, England) · 2025Review
- Cancer-Associated Lymphoid Aggregates in Histology Images: Manual and Deep Learning-Based Quantification Approaches.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The Evolving Landscape of B Cells in Cancer Metastasis.Cancer research · 2023Review
- Microenvironmental and cell intrinsic factors governing human cDC2 differentiation and monocyte reprogramming.Frontiers in immunology · 2023Article
- Singularity and Commonality in Response to SARS-CoV-2 in Lung and Colon Cell Models.International journal of molecular sciences · 2022Article
- Review
- Enriched circulating and tumor-resident TGF-βOncoimmunology · 2022Article
- Review
- AID and APOBECs as Multifaceted Intrinsic Virus-Restricting Factors: Emerging Concepts in the Light of COVID-19.Frontiers in immunology · 2021Article
- Landscape of B lymphocytes and plasma cells in digestive tract carcinomas.Annals of gastroenterologyReview
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
The gut-associated lymphoid tissue represents an integral part of the immune system. Among the powerful players of the mucosa-associated lymphoid tissue are isolated lymphoid structures (ILSs), which as information centers, drive the local (and systemic) adaptive immune responses. Germinal center reactions, taking place within ILSs, involve the coordinated action of various immune cell types with a central role given to B cells. In the current study, we aimed at dissecting the impact of ILSs within non-tumorous colon tissue (NT) on the pathobiology of colorectal cancer (CRC) with metastasis in the liver (CRCLM). In particular, we focused on the immune phenotypes of ILSs and ectopic lymphoid structures (ELSs), built up at matching primary and metastatic tumor sites. We implemented an integrative analysis strategy on the basis of tissue image cytometry and clonality assessment to explore the immune phenotype of ILS/ELS at three tissue entities: NT, CRC, and CRCLM (69 specimens in total). Applying a panel of lineage markers used for immunostaining, we characterized and compared the anatomical features, the cellular composition, the activation, and proliferation status of ILSs and ELSs, and assessed the clinical relevance of staining-derived data sets. Our major discovery was that ILS characteristics at the NT site predefine the immune phenotype of ELSs at CRC and CRCLM. Thereby, B-cell-enriched (CD20) and highly proliferative (Ki67) ILSs and ELSs were found to be associated with improved clinical outcome in terms of survival and enabled patient stratification into risk groups. Moreover, the data revealed a linkage between B-cell clonality at the NT site and the metastatic characteristics of the tumor in the distant liver tissue. Consolidation of immunostaining-based findings with the results of compendium-wide transcriptomic analysis furthermore proposed CD27 as a novel marker of T follicular helper cells within lymphoid structures. Overall, the study nominates the ILS immune phenotype as a novel prognostic marker for patients with metastatic CRC.
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Registered trials
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