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Sialylation of 3-methylcholanthrene-induced fibrosarcoma determines antitumor immune responses during immunoediting.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2010 Nov 15; Vol. 185 (10), pp. 5869-78. Date of Electronic Publication: 2010 Oct 18. - Publication Year :
- 2010
-
Abstract
- Sialylation of tumor cells is involved in various aspects of their malignancy (proliferation, motility, invasion, and metastasis); however, its effect on the process of immunoediting that affects tumor cell immunogenicity has not been studied. We have shown that in mice with impaired immunoediting, such as in IL-1α(-/-) and IFNγ(-/-) mice, 3-methylcholanthrene-induced fibrosarcoma cells are immunogenic and concomitantly bear low levels of surface sialylation, whereas tumor cells derived from wild type mice are nonimmunogenic and bear higher levels of surface sialylation. To study immune mechanisms whose interaction with tumor cells involves surface sialic acid residues, we used highly sialylated 3-methylcholanthrene-induced nonimmunogenic fibrosarcoma cell lines from wild type mice, which were treated with sialidase to mimic immunogenic tumor cell variants. In vivo and in vitro experiments revealed that desialylation of tumor cells reduced their growth and induced cytotoxicity by NK cells. Moreover, sialidase-treated tumor cells better activated NK cells for IFN-γ secretion. The NKG2D-activating receptor on NK cells was shown to be involved in interactions with desialylated ligands on tumor cells, the nature of which is still not known. Thus, the degree of sialylation on tumor cells, which is selected during the process of immunoediting, has possibly evolved as an important mechanism of tumor cells with low intrinsic immunogenicity or select for tumor cells that can evade the immune system or subvert its function. When immunoediting is impaired, such as in IFN-γ(-/-) and IL-1α(-/-) mice, the overt tumor consists of desialylayed tumor cells that interact better with immunosurveillance cells.
- Subjects :
- Animals
Carcinogens toxicity
Cell Proliferation
Cell Separation
Female
Fibrosarcoma chemically induced
Flow Cytometry
Killer Cells, Natural immunology
Methylcholanthrene toxicity
Mice
Mice, Inbred BALB C
Mice, Knockout
Microscopy, Confocal
Microscopy, Fluorescence
NK Cell Lectin-Like Receptor Subfamily K immunology
Cytotoxicity, Immunologic immunology
Fibrosarcoma immunology
Fibrosarcoma metabolism
N-Acetylneuraminic Acid metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 185
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 20956342
- Full Text :
- https://doi.org/10.4049/jimmunol.1001635