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Nat Immunol. 2015 Dec;16(12):1235-44. doi: 10.1038/ni.3290. Epub 2015 Oct 26.

Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma.

Author information

1
Department of Immunology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
2
Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
3
Institute of Virology, Technische Universität München, Helmholtz Zentrum München, Munich, Germany.
4
Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, California, USA.
5
Institute of Surgical Pathology, University and University-Hospital Zurich, Zurich, Switzerland.
6
Research Unit of Radiation Cytogenetics, Helmholtz-Zentrum München, Ingolstädter-Landstrasse, Neuherberg, Germany.
7
Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA.
8
Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
9
Division of Gastroenterology &Hepatology Geneva University Hospital, Geneva, Switzerland.
10
Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
11
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
12
Max Delbrück Center for Molecular Medicine, Berlin, Germany.
13
Division of Chronic Inflammation and Cancer, German Cancer Research Center, Heidelberg, Germany.

Abstract

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.

PMID:
26502405
PMCID:
PMC4653079
DOI:
10.1038/ni.3290
[Indexed for MEDLINE]
Free PMC Article

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