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Eggert, T.* ; Wolter, K.* ; Ji, J.* ; Ma, C.* ; Yevsa, T.* ; Klotz, S.* ; Medina-Echeverz, J.* ; Longerich, T.* ; Forgues, M.* ; Reisinger, F. ; Heikenwälder, M. ; Wang, X.W.* ; Zender, L.* ; Greten, T.F.*

Distinct functions of senescence-associated immune responses in liver tumor surveillance and tumor progression.

Cancer Cell 30, 533-547 (2016)
Verlagsversion Forschungsdaten DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Oncogene-induced senescence causes hepatocytes to secrete cytokines, which induce their immune-mediated clearance to prevent tumor initiation, a process termed "senescence surveillance." However, senescent hepatocytes give rise to hepatocellular carcinomas (HCCs), if the senescence program is bypassed or if senescent cells are not cleared. Here, we show context-specific roles for CCR2(+) myeloid cells in liver cancer. Senescence surveillance requires the recruitment and maturation of CCR2(+) myeloid cells, and CCR2 ablation caused outgrowth of HCC. In contrast, HCC cells block the maturation of recruited myeloid precursors, which, through NK cell inhibition, promote growth of murine HCC and worsen the prognosis and survival of human HCC patients. Thus, while senescent hepatocyte-secreted chemokines suppress liver cancer initiation, they may accelerate the growth of fully established HCC.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Ccl2 ; Ccr2 ; Hcc ; Mdsc ; Nk Cells ; Hepatocellular Carcinoma ; Liver Cancer ; Macrophages ; Myeloid Cells ; Senescence; Hepatocellular-carcinoma Patients; Monocyte Chemoattractant Protein-1; Natural-killer-cells; Suppressor-cells; Nk Cells; T-cells; Cancer; Chemotherapy; Metastasis; Receptor
Sprache deutsch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 1535-6108
e-ISSN 1878-3686
Zeitschrift Cancer Cell
Quellenangaben Band: 30, Heft: 4, Seiten: 533-547 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-551600-001
DOI 10.1016/j.ccell.2016.09.003
WOS ID WOS:000385329800008
PubMed ID 27728804
Erfassungsdatum 2016-10-17
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