A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma.

Autor: Pilcher WC; Coultier Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA., Yao L; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Gonzalez-Kozlova E; Human Immune Monitoring Center, Tisch Cancer Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Pita-Juarez Y; Beth Israel Deaconess Medical Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Karagkouni D; Beth Israel Deaconess Medical Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Acharya CR; MMRF, Norwalk, CT, USA., Michaud ME; Department of Pediatrics, Emory School of Medicine, Atlanta, GA, USA., Hamilton M; MMRF, Norwalk, CT, USA., Nanda S; Beth Israel Deaconess Medical Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Song Y; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Sato K; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Wang JT; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Satpathy S; Department of Biomedical Informatics, Emory School of Medicine, Atlanta, GA, USA., Ma Y; Beth Israel Deaconess Medical Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Schulman J; MMRF, Norwalk, CT, USA., D'Souza D; Human Immune Monitoring Center, Tisch Cancer Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Jayasinghe RG; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Cheloni G; Beth Israel Deaconess Medical Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Bakhtiari M; Department of Pediatrics, Emory School of Medicine, Atlanta, GA, USA., Pabustan N; MMRF, Norwalk, CT, USA., Nie K; Human Immune Monitoring Center, Tisch Cancer Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Foltz JA; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Saldarriaga I; Beth Israel Deaconess Medical Center, Boston, MA, USA., Alaaeldin R; Department of Pediatrics, Emory School of Medicine, Atlanta, GA, USA., Lepisto E; MMRF, Norwalk, CT, USA., Chen R; Human Immune Monitoring Center, Tisch Cancer Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Fiala MA; Bone Marrow Transplantation & Leukemia Section, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA., Thomas BE; Department of Pediatrics, Emory School of Medicine, Atlanta, GA, USA., Cook A; MMRF, Norwalk, CT, USA., Dos Santos JV; Tisch Cancer Institute, Department of Immunology and Immunotherapy, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Chiang IL; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Figueiredo I; Human Immune Monitoring Center, Tisch Cancer Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Fortier J; Bone Marrow Transplantation & Leukemia Section, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA., Slade M; Bone Marrow Transplantation & Leukemia Section, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA., Oh ST; Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.; Immunomonitoring Laboratory, Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA., Rettig MP; Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA., Anderson E; Mayo Clinic, Rochester, MN, USA., Li Y; Mayo Clinic, Rochester, MN, USA., Dasari S; Mayo Clinic, Rochester, MN, USA., Strausbauch MA; Mayo Clinic, Rochester, MN, USA., Simon VA; Mayo Clinic, Rochester, MN, USA., Rahman AH; Human Immune Monitoring Center, Tisch Cancer Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Chen Z; Human Immune Monitoring Center, Tisch Cancer Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Lagana A; Tisch Cancer Institute, Department of Immunology and Immunotherapy, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., DiPersio JF; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA., Rosenblatt J; Beth Israel Deaconess Medical Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Cancer Center & Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA., Kim-Schulze S; Human Immune Monitoring Center, Tisch Cancer Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Dhodapkar MV; Department of Hematology Oncology, Emory School of Medicine, Atlanta, GA, USA.; Winship Cancer Institute, Emory School of Medicine, Atlanta, GA, USA., Lonial S; Department of Pediatrics, Emory School of Medicine, Atlanta, GA, USA.; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta., Kumar S; Mayo Clinic, Rochester, MN, USA., Bhasin SS; Department of Pediatrics, Emory School of Medicine, Atlanta, GA, USA., Kourelis T; Mayo Clinic, Rochester, MN, USA., Vij R; Bone Marrow Transplantation & Leukemia Section, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA.; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA., Avigan D; Beth Israel Deaconess Medical Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Cancer Center & Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA., Cho HJ; MMRF, Norwalk, CT, USA., Mulligan G; MMRF, Norwalk, CT, USA., Ding L; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.; Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, USA., Gnjatic S; Human Immune Monitoring Center, Tisch Cancer Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Vlachos IS; Beth Israel Deaconess Medical Center, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA.; Spatial Technologies Unit, Harvard Medical School Initiative for RNA Medicine, Boston, MA, USA.; Cancer Center & Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA., Bhasin M; Department of Pediatrics, Emory School of Medicine, Atlanta, GA, USA.; Department of Biomedical Informatics, Emory School of Medicine, Atlanta, GA, USA.; Coultier Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 May 17. Date of Electronic Publication: 2024 May 17.
DOI: 10.1101/2024.05.15.593193
Abstrakt: Multiple Myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We established a harmonized consortium to generate an Immune Atlas of MM aimed at informing disease etiology, risk stratification, and potential therapeutic strategies. We generated a transcriptome profile of 1,149,344 single cells from the bone marrow of 263 newly diagnosed patients enrolled in the CoMMpass study and characterized immune and hematopoietic cell populations. Associating cell abundances and gene expression with disease progression revealed the presence of a proinflammatory immune senescence-associated secretory phenotype in rapidly progressing patients. Furthermore, signaling analyses suggested active intercellular communication involving APRIL-BCMA, potentially promoting tumor growth and survival. Finally, we demonstrate that integrating immune cell levels with genetic information can significantly improve patient stratification.
Databáze: MEDLINE