Systematic identification of minor histocompatibility antigens predicts outcomes of allogeneic hematopoietic cell transplantation.


Journal

Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648

Informations de publication

Date de publication:
21 Aug 2024
Historique:
received: 10 07 2023
accepted: 02 07 2024
medline: 22 8 2024
pubmed: 22 8 2024
entrez: 21 8 2024
Statut: aheadofprint

Résumé

T cell alloreactivity against minor histocompatibility antigens (mHAgs)-polymorphic peptides resulting from donor-recipient (D-R) disparity at sites of genetic polymorphisms-is at the core of the therapeutic effect of allogeneic hematopoietic cell transplantation (allo-HCT). Despite the crucial role of mHAgs in graft-versus-leukemia (GvL) and graft-versus-host disease (GvHD) reactions, it remains challenging to consistently link patient-specific mHAg repertoires to clinical outcomes. Here we devise an analytic framework to systematically identify mHAgs, including their detection on HLA class I ligandomes and functional verification of their immunogenicity. The method relies on the integration of polymorphism detection by whole-exome sequencing of germline DNA from D-R pairs with organ-specific transcriptional- and proteome-level expression. Application of this pipeline to 220 HLA-matched allo-HCT D-R pairs demonstrated that total and organ-specific mHAg load could independently predict the occurrence of acute GvHD and chronic pulmonary GvHD, respectively, and defined promising GvL targets, confirmed in a validation cohort of 58 D-R pairs, for the prevention or treatment of post-transplant disease recurrence.

Identifiants

pubmed: 39169264
doi: 10.1038/s41587-024-02348-3
pii: 10.1038/s41587-024-02348-3
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : HL158505
Organisme : NHLBI NIH HHS
ID : R01 HL095791
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL158504
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL158505
Pays : United States
Organisme : Leukemia and Lymphoma Society (Leukemia & Lymphoma Society)
ID : SCOR-22937-22
Organisme : NCI NIH HHS
ID : P01 CA229092
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : 5R25CA174650
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : R50CA251956
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : U24CA270823
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : U01CA27140
Organisme : American Association for Cancer Research (American Association for Cancer Research, Inc.)
ID : 20-40-46-CIER
Organisme : Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)
ID : U19 Al1051731
Organisme : NIAID NIH HHS
ID : U19 AI174967
Pays : United States

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Nicoletta Cieri (N)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Harvard Medical School, Boston, MA, USA.

Nidhi Hookeri (N)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.

Kari Stromhaug (K)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.

Liang Li (L)

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.

Julia Keating (J)

Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.

Paula Díaz-Fernández (P)

Department of Immunology, Instituto de Investigación Sanitaria Princesa (IIS-IP), Hospital Universitario de La Princesa, Madrid, Spain.

Valle Gómez-García de Soria (V)

Department of Hematology, Instituto de Investigación Sanitaria Princesa (IIS-IP), Hospital Universitario de La Princesa, Madrid, Spain.

Jonathan Stevens (J)

Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.

Raphael Kfuri-Rubens (R)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.

Yiren Shao (Y)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.

Kameron A Kooshesh (KA)

Harvard Medical School, Boston, MA, USA.

Kaila Powell (K)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Helen Ji (H)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Gabrielle M Hernandez (GM)

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.

Jennifer Abelin (J)

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.

Susan Klaeger (S)

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Department of Proteomic and Genomic Technologies, Genentech Inc, South San Francisco, CA, USA.

Cleo Forman (C)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.

Karl R Clauser (KR)

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.

Siranush Sarkizova (S)

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.

David A Braun (DA)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Harvard Medical School, Boston, MA, USA.
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA.

Livius Penter (L)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Harvard Medical School, Boston, MA, USA.
Department of Hematology, Oncology, and Tumorimmunology, Campus Virchow Klinikum, Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Haesook T Kim (HT)

Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.

William J Lane (WJ)

Harvard Medical School, Boston, MA, USA.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.

Giacomo Oliveira (G)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Harvard Medical School, Boston, MA, USA.

Leslie S Kean (LS)

Harvard Medical School, Boston, MA, USA.
Division Hematology/Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA.

Shuqiang Li (S)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA, USA.

Kenneth J Livak (KJ)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA, USA.

Steven A Carr (SA)

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.

Derin B Keskin (DB)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Harvard Medical School, Boston, MA, USA.
Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Computer Science, Metropolitan College, Boston University, Boston, MA, USA.
Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Lyngby, Denmark.

Cecilia Muñoz-Calleja (C)

Department of Immunology, Instituto de Investigación Sanitaria Princesa (IIS-IP), Hospital Universitario de La Princesa, Madrid, Spain.
Department of Medicine, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.

Vincent T Ho (VT)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Jerome Ritz (J)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Robert J Soiffer (RJ)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

Donna Neuberg (D)

Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.

Chip Stewart (C)

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.

Gad Getz (G)

Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
Harvard Medical School, Boston, MA, USA.
Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.

Catherine J Wu (CJ)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. catherine_wu@dfci.harvard.edu.
Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA. catherine_wu@dfci.harvard.edu.
Harvard Medical School, Boston, MA, USA. catherine_wu@dfci.harvard.edu.
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. catherine_wu@dfci.harvard.edu.

Classifications MeSH