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

Cancer Cell 30, 533-547 (2016)
Publishers Version Research data DOI
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Keywords 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
Reviewing status