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

Official URL:https://doi.org/10.1038/ni.3290
PubMed:View item in PubMed
Creators Name:Finkin, S. and Yuan, D. and Stein, I. and Taniguchi, K. and Weber, A. and Unger, K. and Browning, J.L. and Goossens, N. and Nakagawa, S. and Gunasekaran, G. and Schwartz, M.E. and Kobayashi, M. and Kumada, H. and Berger, M. and Pappo, O. and Rajewsky, K. and Hoshida, Y. and Karin, M. and Heikenwalder, M. and Ben-Neriah, Y. and Pikarsky, E.
Journal Title:Nature Immunology
Journal Abbreviation:Nat Immunol
Volume:16
Number:12
Page Range:1235-1244
Date:December 2015
Keywords:Adaptive Immunity, Animal Disease Models, Comparative Genomic Hybridization, Cytokines, Hepatocellular Carcinoma, Hepatocytes, I-{kappa} B Kinase, Immunoblotting, In Situ Hybridization, Inbred C57BL Mice, Innate Immunity, Knockout Mice, Liver Neoplasms, Lymphoid Tissue, NF-{kappa} B, Neoplastic Stem Cells, Reverse Transcriptase Polymerase Chain Reaction, Stem Cell Niche, T-Lymphocytes, Transcriptome, Transgenic Mice, Animals, Mice
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-{kappa}B and abolished by depletion of T cells. Such aberrant immunological foci might represent new targets for cancer therapy.
ISSN:1529-2908
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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