Expression of tolerogenic HLA-G molecules in cancer prevents antitumor responses.
In this paper, we focus our attention on the relevance of HLA-G in cancer in the light of our recent advances on the expression and immunological function of HLA-G. Regarding HLA-G function, we recently showed that in addition to its direct inhibitory effects on T, APC and NK function, HLA-G induces suppressor cells via two distinct processes: (i) either by cell differentiation of naïve T cells into lasting suppressor T cells or (ii) by rapid transfer of HLA-G from APC or tumor cells to T or NK cells converting them into temporary HLA-G-positive suppressor cells. Regarding HLA-G expression, we described that tumor-microenvironment factors such as hypoxia, IDO and, TNF-alpha regulate the expression of HLA-G by tumor cells in a way that favors tumor escape from NK lysis. These findings reinforce the role of HLA-G as one mechanism of tumor-driven immune evasion and provide potential targets for testing novel anticancer treatment strategies.
Rouas-Freiss
Nathalie
N
CEA, DSV, I2BM, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, IUH, 1 avenue Claude Vellefaux, 75010 Paris, France. Nathalie.Rouas-Freiss@cea.fr
Moreau
Philippe
P
Menier
Catherine
C
LeMaoult
Joël
J
Carosella
Edgardo D
ED
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015687:Cell Hypoxia; D006680:HLA Antigens / Q000276:immunology* / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007157:Immunologic Surveillance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D019139:Tumor Escape; D000097782:NF-kappaB-Inducing Kinase
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase