Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Carcinogenesis
2014 Aug 01;358:1807-13. doi: 10.1093/carcin/bgu100.
Show Gene links
Show Anatomy links
A critical role of non-classical MHC in tumor immune evasion in the amphibian Xenopus model.
Haynes-Gilmore N
,
Banach M
,
Edholm ES
,
Lord E
,
Robert J
.
???displayArticle.abstract???
Non-classical class Ib (class Ib) genes are found in all jawed vertebrates, including the amphibian Xenopus, which possesses at least 20 distinct Xenopus non-classical class Ib genes (XNCs). As an immune evasion strategy, tumors often downregulate surface expression of classical major histocompatibility complex class Ia molecules. In contrast, cancers commonly express class Ib molecules, presenting an alternative for tumor immune recognition. We characterized a novel XNC, XNC10, functionally similar to CD1d from a class Ia-deficient thymic lymphoid tumor (15/0), which grows aggressively in Xenopus LG-15 cloned animals. To investigate the roles of XNC10 in antitumor immunity, we generated stable 15/0-transfectants with silenced XNC10 mRNA and protein expression. Notably, XNC10 silencing resulted in acute tumor rejection by naturally class Ia-deficient syngeneic tadpoles, with greater potency of rejection in tumors with more efficient XNC10 knockdown. In vivo killing assays shows that the rejection of XNC10-deficient tumors is due to a cell-mediated cytotoxic immune response elicited by the tadpole host. Importantly, priming enhances XNC10-deficient tumor rejection. Flow cytometry reveals that XNC10-deficient tumor rejection is associated with an accumulation of XNC10-restricted invariant T cells and conventional CD8 T cells as well as other leukocytes. Similarly, semisolid tumor grafts in tadpoles also exhibit leukocytes infiltration. These findings suggest that XNC10 allows the 15/0-tumor to escape immune recognition and class Ia-independent cytotoxicity, thus emphasizing the critical roles of class Ibs in tumor immunity.
Bukur,
The role of classical and non-classical HLA class I antigens in human tumors.
2012, Pubmed
Bukur,
The role of classical and non-classical HLA class I antigens in human tumors.
2012,
Pubmed
Chang,
HLA class I defects in malignant lesions: what have we learned?
2003,
Pubmed
Chiang,
The nonclassical major histocompatibility complex molecule Qa-2 protects tumor cells from NK cell- and lymphokine-activated killer cell-mediated cytolysis.
2002,
Pubmed
Chiang,
A nonclassical MHC class I molecule restricts CTL-mediated rejection of a syngeneic melanoma tumor.
2004,
Pubmed
Connor,
Loss of MHC class-I expression in cervical carcinomas.
1990,
Pubmed
Cui,
Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors.
1997,
Pubmed
de Kruijf,
HLA-E and HLA-G expression in classical HLA class I-negative tumors is of prognostic value for clinical outcome of early breast cancer patients.
2010,
Pubmed
Du Pasquier,
In vitro growth of thymic tumor cell lines from Xenopus.
1992,
Pubmed
,
Xenbase
Edholm,
Nonclassical MHC class I-dependent invariant T cells are evolutionarily conserved and prominent from early development in amphibians.
2013,
Pubmed
,
Xenbase
Fisher,
Generation of monoclonal antibodies specific for human kallikrein 2 (hK2) using hK2-expressing tumors.
2002,
Pubmed
Flajnik,
A novel type of class I gene organization in vertebrates: a large family of non-MHC-linked class I genes is expressed at the RNA level in the amphibian Xenopus.
1993,
Pubmed
,
Xenbase
Gleimer,
Stress management: MHC class I and class I-like molecules as reporters of cellular stress.
2003,
Pubmed
Gonçalves,
Classical and non-classical HLA molecules and p16(INK4a) expression in precursors lesions and invasive cervical cancer.
2008,
Pubmed
Goyos,
Novel nonclassical MHC class Ib genes associated with CD8 T cell development and thymic tumors.
2009,
Pubmed
,
Xenbase
Goyos,
Remarkable conservation of distinct nonclassical MHC class I lineages in divergent amphibian species.
2011,
Pubmed
,
Xenbase
Goyos,
Involvement of nonclassical MHC class Ib molecules in heat shock protein-mediated anti-tumor responses.
2007,
Pubmed
,
Xenbase
Hix,
CD1d-expressing breast cancer cells modulate NKT cell-mediated antitumor immunity in a murine model of breast cancer metastasis.
2011,
Pubmed
Ishitani,
The involvement of HLA-E and -F in pregnancy.
2006,
Pubmed
Lepin,
Functional characterization of HLA-F and binding of HLA-F tetramers to ILT2 and ILT4 receptors.
2000,
Pubmed
Lin,
HLA-F expression is a prognostic factor in patients with non-small-cell lung cancer.
2011,
Pubmed
Morales,
Innate immune responses and permissiveness to ranavirus infection of peritoneal leukocytes in the frog Xenopus laevis.
2010,
Pubmed
,
Xenbase
Nedelkovska,
Comparative in vivo study of gp96 adjuvanticity in the frog Xenopus laevis.
2010,
Pubmed
,
Xenbase
Paul,
HLA-G expression in melanoma: a way for tumor cells to escape from immunosurveillance.
1998,
Pubmed
Pilones,
Invariant NKT cells as novel targets for immunotherapy in solid tumors.
2012,
Pubmed
Robert,
Antibody cross-linking of the thymocyte-specific cell surface molecule CTX causes abnormal mitosis and multinucleation of tumor cells.
1997,
Pubmed
,
Xenbase
Robert,
Lymphoid tumors of Xenopus laevis with different capacities for growth in larvae and adults.
1994,
Pubmed
,
Xenbase
Robert,
Ontogeny of CTX expression in xenopus.
1998,
Pubmed
,
Xenbase
Robert,
Phylogenetic conservation of the molecular and immunological properties of the chaperones gp96 and hsp70.
2001,
Pubmed
,
Xenbase
Ugurel,
Soluble human leukocyte antigen--G serum level is elevated in melanoma patients and is further increased by interferon-alpha immunotherapy.
2001,
Pubmed
Wiendl,
A functional role of HLA-G expression in human gliomas: an alternative strategy of immune escape.
2002,
Pubmed
Wolpert,
HLA-E contributes to an immune-inhibitory phenotype of glioblastoma stem-like cells.
2012,
Pubmed
