title: Significant decline in anticancer immune capacity during puberty in the Tasmanian devil.
abstract: Tasmanian devils (Sarcophilus harrisii) are at risk of extinction in the wild due to Devil Facial Tumour Disease (DFTD), a rare contagious cancer. The prevalence of DFTD differs by age class: higher disease prevalence is seen in adults (2-3 years) versus younger devils (<2 years). Here we propose that immunological changes during puberty may play a role in susceptibility to DFTD. We show that the second year of life is a key developmental period for Tasmanian devils, during which they undergo puberty and pronounced changes in the immune system. Puberty coincides with a significant decrease in lymphocyte abundance resulting in a much higher neutrophil:lymphocyte ratio in adults than subadults. Quantitative PCR analysis of gene expression of transcription factors T-bet and GATA-3 and cytokines interferon gamma (IFN-γ) and interleukin 4 (IL-4) revealed a drastic increase in GATA-3 and IL-4 expression during puberty. These changes led to a significantly lower IFN-γ:IL-4 ratio in 2-year-olds than <1 year olds (on average 1.3-fold difference in males and 4.0-fold in females), which reflects a major shift of the immune system towards Th2 responses. These results all indicate that adult devils are expected to have a lower anticancer immune capacity than subadults, which may explain the observed pattern of disease prevalence of DFTD in the wild.
authors.affiliation: School of Life and Environmental Sciences, The University of Sydney, New South Wales, 2006, Australia.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: School of Life and Environmental Sciences, The University of Sydney, New South Wales, 2006, Australia.
authors.forename: Kim
authors.initials: K
authors.lastname: Heasman
authors.affiliation: Department of Primary Industries, Parks, Water and Environment, 134 Macquarie Street, Hobart, Tasmania, 7000, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Peck
authors.affiliation: School of Life and Environmental Sciences, The University of Sydney, New South Wales, 2006, Australia.
authors.forename: Emma
authors.initials: E
authors.lastname: Peel
authors.affiliation: School of Life and Environmental Sciences, The University of Sydney, New South Wales, 2006, Australia.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Gooley
authors.affiliation: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia.|Computational Cancer Biology Program, Peter MacCallum Cancer Centre, Victoria, 3000, Australia.|Department of Medical Biology, University of Melbourne, Victoria, 3010, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, 3010, Australia.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Papenfuss
authors.affiliation: School of Life and Environmental Sciences, The University of Sydney, New South Wales, 2006, Australia.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Hogg
authors.affiliation: School of Life and Environmental Sciences, The University of Sydney, New South Wales, 2006, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Belov
mesh_terms: D000818:Animals; D001835:Body Weight; D005260:Female; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008394:Marsupialia / Q000276:immunology*; D009369:Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism; D011374:Progesterone / Q000097:blood; D012741:Sexual Maturation; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D015847:Interleukin-4; D011374:Progesterone; D007371:Interferon-gamma