Immune surveillance of senescent cells--biological significance in cancer- and non-cancer pathologies.

Cellular senescence, a state of stable growth arrest, can occur in response to various stress stimuli such as telomere shortening, treatment with chemotherapeutic drugs or the aberrant activation of oncogenes. Senescent cells communicate with their environment by secreting various cytokines and growth factors, and it has become clear that this 'secretory phenotype' can have pro- as well as anti-tumorigenic effects. Recent work from our laboratory showed that premalignant, senescent hepatocytes are recognized and cleared through an antigen-specific immune response and that this immune response, designated as 'senescence surveillance' is crucial for tumor suppression in the liver [(Kang,T.W. et al. (2011) Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature, 479, 547-551]. It is an emerging concept that immune responses against senescent cells have a broader biological significance in cancer- as well as non-cancer pathologies and current data suggest that distinct immune responses are engaged to clear senescent cells in different disease settings. In this review article, we will discuss different examples how immune responses against senescent cells are involved to restrict disease progression in cancer- and non-cancer pathologies.

[1]  T. Luedde,et al.  Senescence surveillance of pre-malignant hepatocytes limits liver cancer development , 2011, Nature.

[2]  N. LeBrasseur,et al.  Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders , 2011, Nature.

[3]  J. Lambert,et al.  Immune reactions in benign and malignant melanocytic lesions: lessons for immunotherapy , 2011, Pigment cell & melanoma research.

[4]  E. K. Parkinson,et al.  Senescent mesenchymal cells accumulate in human fibrosis by a telomere‐independent mechanism and ameliorate fibrosis through matrix metalloproteinases , 2011, The Journal of pathology.

[5]  R. Schreiber,et al.  Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion , 2011, Science.

[6]  D. Peeper,et al.  The essence of senescence. , 2010, Genes & development.

[7]  L. Lau,et al.  The Matricellular Protein CCN1/CYR61 Induces Fibroblast Senescence and Restricts Fibrosis in Cutaneous Wound Healing , 2010, Nature Cell Biology.

[8]  J. Campisi,et al.  Inflammatory networks during cellular senescence: causes and consequences. , 2010, Trends in molecular medicine.

[9]  J. Campisi,et al.  Persistent DNA damage signaling triggers senescence-associated inflammatory cytokine secretion , 2009, Nature Cell Biology.

[10]  D. Peeper,et al.  Senescence-messaging secretome: SMS-ing cellular stress , 2009, Nature Reviews Cancer.

[11]  Jean-Philippe Coppé.  Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor , 2009 .

[12]  Judith Campisi,et al.  Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor , 2008, PLoS biology.

[13]  S. Lowe,et al.  Senescence of Activated Stellate Cells Limits Liver Fibrosis , 2008, Cell.

[14]  D. Peeper,et al.  Oncogene-Induced Senescence Relayed by an Interleukin-Dependent Inflammatory Network , 2008, Cell.

[15]  S. Raguz,et al.  Chemokine Signaling via the CXCR2 Receptor Reinforces Senescence , 2008, Cell.

[16]  Michael R. Green,et al.  Oncogenic BRAF Induces Senescence and Apoptosis through Pathways Mediated by the Secreted Protein IGFBP7 , 2008, Cell.

[17]  Carlos Cordon-Cardo,et al.  Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas , 2007, Nature.

[18]  J. Campisi,et al.  Secretion of Vascular Endothelial Growth Factor by Primary Human Fibroblasts at Senescence* , 2006, Journal of Biological Chemistry.

[19]  R. Bernards,et al.  Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence , 2006, Nature Cell Biology.

[20]  S. Lowe,et al.  Defined genetic events associated with the spontaneous in vitro transformation of ElA/Ras-expressing human IMR90 fibroblasts. , 2006, Carcinogenesis.

[21]  P. Nelson,et al.  The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms. , 2006, Cancer research.

[22]  G. Willimsky,et al.  Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance , 2005, Nature.

[23]  S. Lowe,et al.  Senescence comes of age , 2005, Nature Medicine.

[24]  H. Stein,et al.  Oncogene-induced senescence as an initial barrier in lymphoma development , 2005, Nature.

[25]  Jason A. Koutcher,et al.  Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis , 2005, Nature.

[26]  M. Barbacid,et al.  Tumour biology: Senescence in premalignant tumours , 2005, Nature.

[27]  J. Shay,et al.  BRAFE600-associated senescence-like cell cycle arrest of human naevi , 2005, Nature.

[28]  J. Campisi.  Senescent Cells, Tumor Suppression, and Organismal Aging: Good Citizens, Bad Neighbors , 2005, Cell.

[29]  S. Lowe,et al.  Intrinsic tumour suppression , 2004, Nature.

[30]  J. Campisi,et al.  Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation , 2004, Journal of Cell Science.

[31]  Masashi Narita,et al.  Reversal of human cellular senescence: roles of the p53 and p16 pathways , 2003, The EMBO journal.

[32]  R. Bernards,et al.  Reversal of Senescence in Mouse Fibroblasts through Lentiviral Suppression of p53* 210 , 2003, The Journal of Biological Chemistry.

[33]  M. Blasco,et al.  Putting the stress on senescence. , 2001, Current opinion in cell biology.

[34]  J. Campisi,et al.  Senescent fibroblasts promote epithelial cell growth and tumorigenesis: A link between cancer and aging , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[35]  D. Shelton,et al.  Microarray analysis of replicative senescence , 1999, Current Biology.

[36]  D. Woods,et al.  Senescence of human fibroblasts induced by oncogenic Raf. , 1998, Genes & development.

[37]  G. Peters,et al.  Features of replicative senescence induced by direct addition of antennapedia‐p16INK4A fusion protein to human diploid fibroblasts , 1998, FEBS letters.

[38]  S. Lowe,et al.  Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a , 1997, Cell.

[39]  C Roskelley,et al.  A biomarker that identifies senescent human cells in culture and in aging skin in vivo. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[40]  L. Hayflick.  THE LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS. , 1965, Experimental cell research.

[41]  Sunghuen Kim,et al.  A Report of Two Cases , 2008 .