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Single-cell RNA sequencing reveals compromised immune microenvironment in precursor stages of multiple myeloma.
Zavidij, Oksana; Haradhvala, Nicholas J; Mouhieddine, Tarek H; Sklavenitis-Pistofidis, Romanos; Cai, Songjie; Reidy, Mairead; Rahmat, Mahshid; Flaifel, Abdallah; Ferland, Benjamin; Su, Nang K; Agius, Michael P; Park, Jihye; Manier, Salomon; Bustoros, Mark; Huynh, Daisy; Capelletti, Marzia; Berrios, Brianna; Liu, Chia-Jen; He, Meng Xiao; Braggio, Esteban; Fonseca, Rafael; Maruvka, Yosef E; Guerriero, Jennifer L; Goldman, Melissa; Van Allen, Eliezer M; McCarroll, Steven A; Azzi, Jamil; Getz, Gad; Ghobrial, Irene M.
Afiliação
  • Zavidij O; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Haradhvala NJ; Harvard Medical School, Boston, MA, USA.
  • Mouhieddine TH; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Sklavenitis-Pistofidis R; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Cai S; Massachusetts General Hospital, Boston, MA, USA.
  • Reidy M; Harvard Biophysics Graduate Program, Harvard University, Boston, MA, USA.
  • Rahmat M; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Flaifel A; Harvard Medical School, Boston, MA, USA.
  • Ferland B; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Su NK; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Agius MP; Harvard Medical School, Boston, MA, USA.
  • Park J; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Manier S; Harvard Medical School, Boston, MA, USA.
  • Bustoros M; Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Boston, MA, USA.
  • Huynh D; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Capelletti M; Harvard Medical School, Boston, MA, USA.
  • Berrios B; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Liu CJ; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • He MX; Harvard Medical School, Boston, MA, USA.
  • Braggio E; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Fonseca R; Harvard Medical School, Boston, MA, USA.
  • Maruvka YE; Specialized Histopathology Core, Brigham and Women's Hospital, Boston, MA, USA.
  • Guerriero JL; Specialized Histopathology Core, Brigham and Women's Hospital, Boston, MA, USA.
  • Goldman M; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Van Allen EM; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • McCarroll SA; Harvard Medical School, Boston, MA, USA.
  • Azzi J; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Getz G; Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Ghobrial IM; Harvard Medical School, Boston, MA, USA.
Nat Cancer ; 1(5): 493-506, 2020 05.
Article em En | MEDLINE | ID: mdl-33409501
ABSTRACT
Precursor states of Multiple Myeloma (MM) and its native tumor microenvironment need in-depth molecular characterization to better stratify and treat patients at risk. Using single-cell RNA sequencing of bone marrow cells from precursor stages, MGUS and smoldering myeloma (SMM), to full-blown MM alongside healthy donors, we demonstrate early immune changes during patient progression. We find NK cell abundance is frequently increased in early stages, and associated with altered chemokine receptor expression. As early as SMM, we show loss of GrK+ memory cytotoxic T-cells, and show their critical role in MM immunosurveillance in mouse models. Finally, we report MHC class II dysregulation in CD14+ monocytes, which results in T cell suppression in vitro. These results provide a comprehensive map of immune changes at play over the evolution of pre-malignant MM, which will help develop strategies for immune-based patient stratification.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Gamopatia Monoclonal de Significância Indeterminada / Mieloma Múltiplo Latente / Mieloma Múltiplo Limite: Animals / Humans Idioma: En Revista: Nat Cancer Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Gamopatia Monoclonal de Significância Indeterminada / Mieloma Múltiplo Latente / Mieloma Múltiplo Limite: Animals / Humans Idioma: En Revista: Nat Cancer Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos