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

Autor:	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., 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., 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., Li L; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA., Keating J; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA., Díaz-Fernández P; Department of Immunology, Instituto de Investigación Sanitaria Princesa (IIS-IP), Hospital Universitario de La Princesa, Madrid, Spain., Gómez-García de Soria V; Department of Hematology, Instituto de Investigación Sanitaria Princesa (IIS-IP), Hospital Universitario de La Princesa, Madrid, Spain., Stevens J; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., 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., 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., Kooshesh KA; Harvard Medical School, Boston, MA, USA., Powell K; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Ji H; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Hernandez GM; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA., Abelin J; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA., 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., Forman C; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA., Clauser KR; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA., Sarkizova S; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA., 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., 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., Kim HT; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA., Lane WJ; Harvard Medical School, Boston, MA, USA.; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., 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., Kean LS; Harvard Medical School, Boston, MA, USA.; Division Hematology/Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA., Li S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA, USA., Livak KJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.; Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA, USA., Carr SA; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA., 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., 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., 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., 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., 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., Neuberg D; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA., Stewart C; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA., 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., 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.
Jazyk:	angličtina
Zdroj:	Nature biotechnology [Nat Biotechnol] 2024 Aug 21. Date of Electronic Publication: 2024 Aug 21.
DOI:	10.1038/s41587-024-02348-3
Abstrakt:	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. (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze:	MEDLINE
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