HLA-G1 and HLA-G5 active dimers are present in malignant cells and effusions: the influence of the tumor microenvironment.
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.
CEA, IMETI, Service de Recherches en Hemato-Immunologie, Paris, France.
Sonia
S
Zilberman
Chantal
C
Schenowitz
Sophie
S
Agaugué
Favier
F
Benoît
Béatrice
B
Riteau
Roman
R
Rouzier
Edgardo D
ED
Carosella
Nathalie
N
Rouas-Freiss
Catherine
C
Menier
D045744:Cell Line, Tumor; D059951:HLA-G Antigens / Q000737:chemistry*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D055503:Protein Multimerization; D059016:Tumor Microenvironment; D001613:beta 2-Microglobulin / Q000502:physiology
D059951:HLA-G Antigens; D001613:beta 2-Microglobulin; D016899:Interferon-beta; D007371:Interferon-gamma