期刊
PATHOGENS
卷 11, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/pathogens11030351
关键词
transmissible cancer; Tasmanian devils; MHC class I; nonclassical; immune evasion
类别
资金
- Morris Animal Foundation [D18ZO-104]
- Australian Research Council [DP180100520, DE170101116, LP170101101]
- Save the Tasmanian Devil Appeal
- Wildcare Inc.
- Gerald Kerkut Charitable Trust
- University of Southampton
- Australian Research Council [DE170101116] Funding Source: Australian Research Council
Devil facial tumour disease (DFTD) is a transmissible cancer in Tasmanian devils. It evades the host immune response by reducing major histocompatibility complex class I (MHC-I) expression, but the absence of MHC-I should activate natural killer (NK) cells. The study also found the expression of nonclassical MHC-I Saha-UD in DFTD tumors, which may serve as an immunosuppressive mechanism.
Devil facial tumour disease (DFTD) is a transmissible cancer that has circulated in the Tasmanian devil population for >25 years. Like other contagious cancers in dogs and devils, the way DFTD escapes the immune response of its host is a central question to understanding this disease. DFTD has a low major histocompatibility complex class I (MHC-I) expression due to epigenetic modifications, preventing host immune recognition of mismatched MHC-I molecules by T cells. However, the total MHC-I loss should result in natural killer (NK) cell activation due to the 'missing self'. Here, we have investigated the expression of the nonclassical MHC-I, SahaUD as a potential regulatory or suppressive mechanism for DFTD. A monoclonal antibody was generated against the devil Saha-UD that binds recombinant Saha-UD by Western blot, with limited crossreactivity to the classical MHC-I, Saha-UC and nonclassical Saha-UK. Using this antibody, we confirmed the expression of Saha-UD in 13 DFTD tumours by immunohistochemistry (n = 15) and demonstrated that Saha-UD expression is heterogeneous, with 12 tumours showing intratumour heterogeneity. Immunohistochemical staining for the Saha-UD showed distinct patterns of expression when compared with classical MHC-I molecules. The nonclassical Saha-UD expression by DFTD tumours in vivo may be a mechanism for immunosuppression, and further work is ongoing to characterise its ligand on immune cells.
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