Expression of tolerogenic HLA-G molecules in cancer prevents antitumor responses

• Published in: Seminars in cancer biology Vol. 17; no. 6; pp. 413 - 421
• Main Authors: Rouas-Freiss, Nathalie, Moreau, Philippe, Menier, Catherine, LeMaoult, Joël, Carosella, Edgardo D
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2007
• Subjects: CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Hypoxia; Hematology, Oncology and Palliative Medicine; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; HLA Antigens - immunology; HLA Antigens - metabolism; HLA-G; HLA-G Antigens; Humans; IDO; Immunologic Surveillance; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Neoplasms - immunology; Neoplasms - metabolism; NF-kappaB-Inducing Kinase; NF-κB; Protein Serine-Threonine Kinases - metabolism; Suppressor T cells; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; TNF-α; Trogocytosis; Tumor Escape; Suppressor T cells; NF-κB; TNF-α; IDO; Tumor escape; Trogocytosis; HLA-G
• ISSN: 1044-579X; 1096-3650
• DOI: 10.1016/j.semcancer.2007.07.003

Abstract 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-α 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.