Published in
Nature Research, Nature Communications, 1(10), 2019
DOI: 10.1038/s41467-019-08871-1
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Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT
,
Filippo Cortesi ,
Pantaleo De Simone,
Cristina Toffalori,
Valentina Gambacorta,
Raffaella Greco,
Jacopo Peccatori,
Monica Casucci,
Giulia Casorati,
Paolo Dellabona,
Masahiro Onozawa
and other authors.
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Abstract
AbstractThe 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 (TSCM) 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-TSCM 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.