Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma
Open accessAbstract
Ectopic lymphoid-like structures (ELSs) are often observed in cancer, yet their function is obscure. Although ELSs signify good prognosis in certain malignancies, we found that hepatic ELSs indicated poor prognosis for hepatocellular carcinoma (HCC). We studied an HCC mouse model that displayed abundant ELSs and found that they constituted immunopathological microniches wherein malignant hepatocyte progenitor cells appeared and thrived in a complex cellular and cytokine milieu until gaining self-sufficiency. The egress of progenitor cells and tumor formation were associated with the autocrine production of cytokines previously provided by the niche. ELSs developed via cooperation between the innate immune system and adaptive immune system, an event facilitated by activation of the transcription factor NF-κB and abolished by depletion of T cells. Such aberrant immunological foci might represent new targets for cancer therapy.
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B cells have a dual role in hepatocellular carcinoma immunobiology, promoting tumour development while also enhancing immunotherapy response.
“B cells have a dual role in HCC immunobiology, promoting tumour development but also enhancing the response to immunotherapy by producing antitumour antibodies and activating T cells65.”
From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [65]
The Results section, “ELSs express high amounts of growth promoting cytokines” (page unavailable), finds that B lymphocytes express LTβ within tumor-promoting ectopic lymphoid structures, supporting a role in HCC development. The paper does not report that B cells enhance immunotherapy response by producing antitumour antibodies or activating T cells. (LLM, conf=0.86)
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“Indeed, liver ELS may function as microniches for tumor development (26).”
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- Authors
- Finkin, S., Yuan, D., Stein, I., Taniguchi, K., Weber, A., Unger, K., Browning, J. L., Goossens, N., Nakagawa, S., Gunasekaran, G., Schwartz, M. E., Kobayashi, M., Kumada, H., Berger, M., Pappo, O., Rajewsky, K., Hoshida, Y., Karin, M., Heikenwalder, M., Ben-Neriah, Y., & Pikarsky, E.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Helmholtz Munich (DE)
- University of California San Diego (US)
- University of Zurich (CH)
- Boston University (US)
- University of Geneva (CH)
- Tisch Cancer Institute (US)
- Mount Sinai Hospital (US)
- Toranomon Hospital (JP)
- Hadassah Medical Center (IL)
- Max Delbrück Center (DE)
- Corresponding author
- Pikarsky, Eli
- ORCID
- Venue
- Nature Immunology
- Published
- 2015-12
- Volume
- 16
- Issue
- 12
- Pages
- 1235-1244
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC4653079
- OpenAlex
- W2185780593
- Cited by
- 433
- References
- 52
- Citations by year
- 2026: 40 · 2025: 45 · 2024: 51 · 2023: 47 · 2022: 62 · 2021: 51 · 2020: 29 · 2019: 30 · 2018: 32 · 2017: 18 · 2016: 25 · 2015: 2
- FWCI
- 12.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Cancer Institute (R01CA118165, CA118165, P30CA196521)
- National Institute of Allergy and Infectious Diseases (AI0043477, R01AI043477, R37AI043477)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK099558, DK099558)
- National Institute of Environmental Health Sciences (P42ES010337, ES 010337)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- tertiary lymphoid structures, hepatocellular carcinoma, tumor progenitor cells, tumor microenvironment, NF-κB, T cells, chronic inflammation, prognosis, cancer therapy targets
- MeSH terms
- Animals, Disease Models, Animal, Carcinoma, Hepatocellular, Humans, Immunity, Innate, Liver Neoplasms, Lymphoid Tissue, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocytes, Neoplastic Stem Cells, Immunoblotting, Cytokines, NF-kappa B, In Situ Hybridization, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Hepatocytes, I-kappa B Kinase, Comparative Genomic Hybridization, Stem Cell Niche, Adaptive Immunity, Transcriptome
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