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Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT

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Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT. / 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.

in: NAT COMMUN, Jahrgang 10, Nr. 1, 25.03.2019, S. 1065.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Noviello, M, Manfredi, F, Ruggiero, E, Perini, T, Oliveira, G, Cortesi, F, De Simone, P, Toffalori, C, Gambacorta, V, Greco, R, Peccatori, J, Casucci, M, Casorati, G, Dellabona, P, Onozawa, M, Teshima, T, Griffioen, M, Halkes, CJM, Falkenburg, JHF, Stölzel, F, Altmann, H, Bornhäuser, M, Waterhouse, M, Zeiser, R, Finke, J, Cieri, N, Bondanza, A, Vago, L, Ciceri, F & Bonini, C 2019, 'Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT', NAT COMMUN, Jg. 10, Nr. 1, S. 1065. https://doi.org/10.1038/s41467-019-08871-1

APA

Noviello, M., Manfredi, F., Ruggiero, E., Perini, T., Oliveira, G., Cortesi, F., De Simone, P., Toffalori, C., Gambacorta, V., Greco, R., Peccatori, J., Casucci, M., Casorati, G., Dellabona, P., Onozawa, M., Teshima, T., Griffioen, M., Halkes, C. J. M., Falkenburg, J. H. F., ... Bonini, C. (2019). Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT. NAT COMMUN, 10(1), 1065. https://doi.org/10.1038/s41467-019-08871-1

Vancouver

Noviello M, Manfredi F, Ruggiero E, Perini T, Oliveira G, Cortesi F et al. Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT. NAT COMMUN. 2019 Mär 25;10(1):1065. https://doi.org/10.1038/s41467-019-08871-1

Bibtex

@article{2cb250eaad5a4b7099093c5015b1d905,
title = "Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT",
abstract = "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 (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.",
keywords = "Adult, Antigens, CD/genetics, Antineoplastic Agents/therapeutic use, Bone Marrow Cells/immunology, CTLA-4 Antigen/genetics, Clonal Anergy, Female, Gene Expression Regulation, Leukemic, Glucocorticoid-Induced TNFR-Related Protein/genetics, Hematopoietic Stem Cell Transplantation, Hepatitis A Virus Cellular Receptor 2/genetics, Humans, Immunologic Memory/genetics, Leukemia, Myeloid, Acute/genetics, Male, Middle Aged, Programmed Cell Death 1 Receptor/genetics, Receptors, KIR/genetics, Recurrence, Remission Induction, Retrospective Studies, Signal Transduction, Signaling Lymphocytic Activation Molecule Family/genetics, T-Lymphocytes/immunology, Transplantation, Homologous",
author = "Maddalena Noviello and Francesco Manfredi and Eliana Ruggiero and Tommaso Perini and Giacomo Oliveira and Filippo Cortesi and {De Simone}, Pantaleo and Cristina Toffalori and Valentina Gambacorta and Raffaella Greco and Jacopo Peccatori and Monica Casucci and Giulia Casorati and Paolo Dellabona and Masahiro Onozawa and Takanori Teshima and Marieke Griffioen and Halkes, {Constantijn J M} and Falkenburg, {J H F} and Friedrich St{\"o}lzel and Heidi Altmann and Martin Bornh{\"a}user and Miguel Waterhouse and Robert Zeiser and J{\"u}rgen Finke and Nicoletta Cieri and Attilio Bondanza and Luca Vago and Fabio Ciceri and Chiara Bonini",
year = "2019",
month = mar,
day = "25",
doi = "10.1038/s41467-019-08871-1",
language = "English",
volume = "10",
pages = "1065",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT

AU - Noviello, Maddalena

AU - Manfredi, Francesco

AU - Ruggiero, Eliana

AU - Perini, Tommaso

AU - Oliveira, Giacomo

AU - Cortesi, Filippo

AU - De Simone, Pantaleo

AU - Toffalori, Cristina

AU - Gambacorta, Valentina

AU - Greco, Raffaella

AU - Peccatori, Jacopo

AU - Casucci, Monica

AU - Casorati, Giulia

AU - Dellabona, Paolo

AU - Onozawa, Masahiro

AU - Teshima, Takanori

AU - Griffioen, Marieke

AU - Halkes, Constantijn J M

AU - Falkenburg, J H F

AU - Stölzel, Friedrich

AU - Altmann, Heidi

AU - Bornhäuser, Martin

AU - Waterhouse, Miguel

AU - Zeiser, Robert

AU - Finke, Jürgen

AU - Cieri, Nicoletta

AU - Bondanza, Attilio

AU - Vago, Luca

AU - Ciceri, Fabio

AU - Bonini, Chiara

PY - 2019/3/25

Y1 - 2019/3/25

N2 - 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 (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.

AB - 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 (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.

KW - Adult

KW - Antigens, CD/genetics

KW - Antineoplastic Agents/therapeutic use

KW - Bone Marrow Cells/immunology

KW - CTLA-4 Antigen/genetics

KW - Clonal Anergy

KW - Female

KW - Gene Expression Regulation, Leukemic

KW - Glucocorticoid-Induced TNFR-Related Protein/genetics

KW - Hematopoietic Stem Cell Transplantation

KW - Hepatitis A Virus Cellular Receptor 2/genetics

KW - Humans

KW - Immunologic Memory/genetics

KW - Leukemia, Myeloid, Acute/genetics

KW - Male

KW - Middle Aged

KW - Programmed Cell Death 1 Receptor/genetics

KW - Receptors, KIR/genetics

KW - Recurrence

KW - Remission Induction

KW - Retrospective Studies

KW - Signal Transduction

KW - Signaling Lymphocytic Activation Molecule Family/genetics

KW - T-Lymphocytes/immunology

KW - Transplantation, Homologous

U2 - 10.1038/s41467-019-08871-1

DO - 10.1038/s41467-019-08871-1

M3 - SCORING: Journal article

C2 - 30911002

VL - 10

SP - 1065

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -