HLA-G1 and HLA-G5 active dimers are present in malignant cells and effusions: The influence of the tumor microenvironment
| Autor: | Benoit Favier, Roman Rouzier, Nathalie Rouas-Freiss, Catherine Menier, Sonia Zilberman, Béatrice Riteau, Chantal Schenowitz, Sophie Agaugué, Edgardo D. Carosella |
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| Rok vydání: | 2012 |
| Předmět: |
0303 health sciences
Tumor microenvironment medicine.medical_treatment Immunology Cancer Human leukocyte antigen Biology medicine.disease 3. Good health 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cancer immunotherapy Tumor progression HLA-G medicine Cancer research Immunology and Allergy Cytotoxic T cell 030304 developmental biology 030215 immunology |
| Zdroj: | European Journal of Immunology. 42:1599-1608 |
| ISSN: | 0014-2980 |
| DOI: | 10.1002/eji.201141761 |
| Popis: | Dimers of the nonclassical HLA-G class I molecule have recently been shown to be active structures that mediate inhibition of NK-cell cytotoxic activity through interaction with the immunoglobulin-like transcript (ILT)-2 inhibitory receptor. However, this has only been proven in trophoblasts and HLA-G transfectants. Here, we document for the first time the existence of HLA-G dimers in cancer. Indeed, we identified both surface and soluble HLA-G dimers in tumor cells and malignant ascites respectively. Interestingly, factors from the tumor microenvironment, such as interferons, enhanced the formation of HLA-G dimers and increased the protection of tumors from NK cell-mediated lysis. These data emphasize the impact of HLA-G conformation on its efficiency at inhibiting the antitumor response and thus favoring tumor progression. In view of these results, the effect of the tumor microenvironment on upregulation of HLA-G function deserves particular attention when designing cancer immunotherapy protocols. |
| Databáze: | OpenAIRE |
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