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

Maddalena Noviello, Francesco Manfredi, Eliana Ruggiero, Tommaso Perini, Giacomo Oliveira, Filippo Cortesi, Pantaleo Simone, Cristina Toffalori, Valentina Gambacorta, Raffaella Greco, Jacopo Peccatori, Monica Casucci, Giulia Casorati, Paolo Dellabona, Masahiro Onozawa, Takanori Teshima, Marieke Griffioen, Constantijn J. M. Halkes, J. H. F. Falkenburg, Friedrich Stölzel, Heidi Altmann, Martin Bornhäuser, Miguel Waterhouse, Robert Zeiser, Jürgen Finke, Nicoletta Cieri, Attilio Bondanza, Luca Vago, Fabio Ciceri and Chiara Bonini ()
Additional contact information
Maddalena Noviello: IRCCS San Raffaele Scientific Institute, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit
Francesco Manfredi: IRCCS San Raffaele Scientific Institute, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit
Eliana Ruggiero: IRCCS San Raffaele Scientific Institute, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit
Tommaso Perini: IRCCS San Raffaele Scientific Institute, Hematology and Hematopoietic Stem Cell Transplantation Unit
Giacomo Oliveira: IRCCS San Raffaele Scientific Institute, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit
Filippo Cortesi: IRCCS San Raffaele Scientific Institute, Division of Immunology, Transplantation and Infectious Diseases, Experimental Immunology Unit
Pantaleo Simone: IRCCS San Raffaele Scientific Institute, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit
Cristina Toffalori: IRCCS San Raffaele Scientifc Institute, Division of Immunology, Transplantation and Infectious Disease, Unit of Immunogenetics, Leukemia Genomics and Immunobiology
Valentina Gambacorta: IRCCS San Raffaele Scientifc Institute, Division of Immunology, Transplantation and Infectious Disease, Unit of Immunogenetics, Leukemia Genomics and Immunobiology
Raffaella Greco: IRCCS San Raffaele Scientific Institute, Hematology and Hematopoietic Stem Cell Transplantation Unit
Jacopo Peccatori: IRCCS San Raffaele Scientific Institute, Hematology and Hematopoietic Stem Cell Transplantation Unit
Monica Casucci: IRCCS San Raffaele Scientific Institute, Division of Immunology, Transplantation and Infectious Diseases, Innovative Immunotherapies Unit
Giulia Casorati: IRCCS San Raffaele Scientific Institute, Division of Immunology, Transplantation and Infectious Diseases, Experimental Immunology Unit
Paolo Dellabona: IRCCS San Raffaele Scientific Institute, Division of Immunology, Transplantation and Infectious Diseases, Experimental Immunology Unit
Masahiro Onozawa: Hokkaido University Faculty of Medicine, Graduate School of Medicine, Department of Hematology
Takanori Teshima: Hokkaido University Faculty of Medicine, Graduate School of Medicine, Department of Hematology
Marieke Griffioen: Leiden University Medical Center (LUMC), Department of Hematology
Constantijn J. M. Halkes: Leiden University Medical Center (LUMC), Department of Hematology
J. H. F. Falkenburg: Leiden University Medical Center (LUMC), Department of Hematology
Friedrich Stölzel: University Hospital Carl Gustav Carus Dresden, Technical University Dresden
Heidi Altmann: University Hospital Carl Gustav Carus Dresden, Technical University Dresden
Martin Bornhäuser: University Hospital Carl Gustav Carus Dresden, Technical University Dresden
Miguel Waterhouse: University of Freiburg Medical Center, Department of Hematology, Oncology and Stem Cell Transplantation
Robert Zeiser: University of Freiburg Medical Center, Department of Hematology, Oncology and Stem Cell Transplantation
Jürgen Finke: University of Freiburg Medical Center, Department of Hematology, Oncology and Stem Cell Transplantation
Nicoletta Cieri: IRCCS San Raffaele Scientific Institute, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit
Attilio Bondanza: IRCCS San Raffaele Scientific Institute, Division of Immunology, Transplantation and Infectious Diseases, Innovative Immunotherapies Unit
Luca Vago: IRCCS San Raffaele Scientifc Institute, Division of Immunology, Transplantation and Infectious Disease, Unit of Immunogenetics, Leukemia Genomics and Immunobiology
Fabio Ciceri: IRCCS San Raffaele Scientific Institute, Hematology and Hematopoietic Stem Cell Transplantation Unit
Chiara Bonini: IRCCS San Raffaele Scientific Institute, Division of Immunology, Transplantation, and Infectious Diseases, Experimental Hematology Unit

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-08871-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08871-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-08871-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().