Senescence surveillance of pre-malignant hepatocytes limits liver cancer development.

[Immanuel kant]

Maybe decreased immune surveillance changes with aging underlie the
accumulation of senescent cells.

Nature. 2011 Nov 9;479(7374):547-51. doi: 10.1038/nature10599.
Senescence surveillance of pre-malignant hepatocytes limits liver
cancer development. Kang TW, Yevsa T, Woller N, Hoenicke L, Wuestefeld
T, Dauch D, Hohmeyer A, Gereke M, Rudalska R, Potapova A, Iken M,
Vucur M, Weiss S, Heikenwalder M, Khan S, Gil J, Bruder D, Manns M,
Schirmacher P, Tacke F, Ott M, Luedde T, Longerich T, Kubicka S,
Zender L. SourceHelmholtz Centre for Infection Research,
Inhoffenstrasse 7, 38124 Braunschweig, Germany. Abstract Upon the
aberrant activation of oncogenes, normal cellscan enter the cellular
senescence program, a state of stable cell-cycle arrest, which
represents an important barrier against tumour development in vivo.
Senescent cellscommunicate with their environment by secreting various
cytokines and growth factors, and it was reported that this 'secretory
phenotype' can have pro- as well as anti-tumorigenic effects. Here we
show that oncogene-induced senescence occurs in otherwise normal
murine hepatocytes in vivo. Pre-malignant senescenthepatocytes secrete
chemo- and cytokines and are subject to immune-mediated clearance
(designated as 'senescence surveillance'), which depends on an intact
CD4(+) T-cell-mediated adaptive immune response. Impaired immune
surveillance of pre-malignant senescenthepatocytes results in the
development of murine hepatocellular carcinomas (HCCs), thus showing
that senescence surveillance is important for tumour suppression in
vivo. In accordance with these observations, ras-specific Th1
lymphocytes could be detected in mice, in which oncogene-induced
senescence had been triggered by hepatic expression of Nras(G12V). We
also found that CD4(+) T cells require monocytes/macrophages to
execute the clearance of senescenthepatocytes. Our study indicates
that senescence surveillance represents an important extrinsic
component of the senescence anti-tumour barrier, and illustrates how
the cellular senescence program is involved in tumour immune
surveillance by mounting specific immune responses against antigens
expressed in pre-malignant senescent cells. ©2011 Macmillan Publishers
Limited. All rights reserved Comment in Nat Rev Cancer. 2012 Jan;12(1):
6. Nature. 2011 Nov 24;479(7374):481-2. PMID: 22080947 [PubMed