{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:06:31Z","timestamp":1791295591853,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,4,7]],"date-time":"2014-04-07T00:00:00Z","timestamp":1396828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"CEA, Region Ile de France and Fondation pour la Recherche Medicale"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:p>Human leukocyte antigen\u2010G (HLA\u2010G) expression by tumors has been evidenced in numerous malignancies in association with poor prognosis and resistance to immunotherapy in humans. Particularly, soluble form of HLA\u2010G was measured at high concentrations in malignant effusions and plasma from cancer patients, and inhibits antitumor immune cells <jats:italic>in vitro<\/jats:italic> through interaction with immunoglobulin\u2010like transcript (ILT) receptors. Nevertheless, <jats:italic>in vivo<\/jats:italic> study demonstrating that HLA\u2010G secretion by tumor cells allows their escape from immunosurveillance remained to be established. Despite nondescribed murine homolog, direct functional interaction of HLA\u2010G with murine paired immunoglobulin\u2010like receptor (PIR)\u2010B, ortholog of human ILT receptors, enables to investigate its role <jats:italic>in vivo<\/jats:italic>. Immunocompetent mice were injected either with syngeneic tumor cells co\u2010expressing HLA\u2010G5, the main soluble HLA\u2010G isoform, and the conformation stabilizer human \u03b22\u2010microglubulin (h\u03b22m), or with h\u03b22m<jats:sup>+<\/jats:sup>HLA\u2010G5<jats:sup>\u2212<\/jats:sup> tumor cells. h\u03b22m expressed at both tumor cell surface acted as a tumor antigen triggering a specific humoral response. Interestingly, although h\u03b22m<jats:sup>+<\/jats:sup>HLA\u2010G5<jats:sup>\u2212<\/jats:sup> tumors were rejected, secreted HLA\u2010G5 provided h\u03b22m<jats:sup>+<\/jats:sup>HLA\u2010G5<jats:sup>+<\/jats:sup> tumors a protection against h\u03b22m\u2010elicited immune rejection, enabling such immunogenic tumors to grow similarly to a poorly immunogenic tumor. HLA\u2010G5 tumor expression was associated with local and peripheral immunosuppression, characterized by dampened anti\u2010h\u03b22m B\u2010cell response, quantitative and functional T\u2010and B\u2010cell defects, accumulation of myeloid\u2010derived suppressor cells able to inhibit T\u2010cell proliferation and reduced T\u2010 and B\u2010cell tumor infiltrate. Our study provides the first <jats:italic>in vivo<\/jats:italic> proof that soluble HLA\u2010G counteracts tumor rejection and reinforces the importance to consider HLA\u2010G as a promising target to optimize current cancer immunotherapies.<\/jats:p>","DOI":"10.1002\/ijc.28845","type":"journal-article","created":{"date-parts":[[2014,3,13]],"date-time":"2014-03-13T07:16:43Z","timestamp":1394695003000},"page":"2107-2117","source":"Crossref","is-referenced-by-count":75,"title":["<i>In vivo<\/i> evidence that secretion of HLA\u2010G by immunogenic tumor cells allows their evasion from immunosurveillance"],"prefix":"10.1002","volume":"135","author":[{"given":"Laure","family":"Loumagne","sequence":"first","affiliation":[{"name":"CEA IMETI Service de Recherches en Hemato\u2010Immunologie (SRHI), Hopital Saint\u2010Louis Paris France"},{"name":"Institut Universitaire d'Hematologie (IUH), Hopital Saint\u2010Louis, UMR_E5, Universite Paris\u2010Diderot\u2010Paris\u20107 Paris 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