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Noviello, Maddalena; Manfredi, Francesco; Ruggiero, Eliana; Perini, Tommaso; Oliveira, Giacomo; Cortesi, Filippo; De Simone, Pantaleo; Toffalori, Cristina; Gambacorta, Valentina; Greco, Raffaella; Peccatori, Jacopo; Casucci, Monica; Casorati, Giulia; Dellabona, Paolo; Onozawa, Masahiro; Teshima, Takanori; Griffioen, Marieke; Halkes, Constantijn J M; Falkenburg, J H F; Stölzel, Friedrich; Altmann, Heidi; Bornhäuser, Martin; Waterhouse, Miguel; Zeiser, Robert; Finke, Jürgen; Cieri, Nicoletta; Bondanza, Attilio; Vago, Luca; Ciceri, Fabio; Bonini, Chiara
Nature communications, 03/2019, Letnik: 10, Številka: 1Journal Article
The major cause of death after allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for acute myeloid leukemia (AML) is disease relapse. We investigated the expression of Inhibitory Receptors (IR; PD-1/CTLA-4/TIM-3/LAG-3/2B4/KLRG1/GITR) on T cells infiltrating the bone marrow (BM) of 32 AML patients relapsing (median 251 days) or maintaining complete remission (CR; median 1 year) after HSCT. A higher proportion of early-differentiated Memory Stem (T ) and Central Memory BM-T cells express multiple IR in relapsing patients than in CR patients. Exhausted BM-T cells at relapse display a restricted TCR repertoire, impaired effector functions and leukemia-reactive specificities. In 57 patients, early detection of severely exhausted (PD-1 Eomes T-bet ) BM-T predicts relapse. Accordingly, leukemia-specific T cells in patients prone to relapse display exhaustion markers, absent in patients maintaining long-term CR. These results highlight a wide, though reversible, immunological dysfunction in the BM of AML patients relapsing after HSCT and suggest new therapeutic opportunities for the disease.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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