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

Shlomi Finkin, Detian Yuan, Ilan Stein, Koji Taniguchi, Achim Weber, Kristian Unger, Jeffrey L. Browning, Nicolas Goossens, Shigeki Nakagawa, Ganesh Gunasekaran, Myron E. Schwartz, Masahiro Kobayashi, Hiromitsu Kumada, Michael Berger, Orit Pappo, Klaus Rajewsky, Yujin Hoshida, Michael Karin, Mathias Heikenwalder, Yinon Ben-NeriahEli Pikarsky

Research output: Contribution to journalArticle

99 Scopus citations

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-? B and abolished by depletion of T cells. Such aberrant immunological foci might represent new targets for cancer therapy.

Original languageEnglish (US)
Pages (from-to)1235-1244
Number of pages10
JournalNature immunology
Volume16
Issue number12
DOIs
StatePublished - Dec 1 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    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., ... Pikarsky, E. (2015). Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma. Nature immunology, 16(12), 1235-1244. https://doi.org/10.1038/ni.3290