Single-cell RNA sequencing reveals compromised immune microenvironment in precursor stages of multiple myeloma

Oksana Zavidij, Nicholas J. Haradhvala, Tarek H. Mouhieddine, Romanos Sklavenitis-Pistofidis, Songjie Cai, Mairead Reidy, Mahshid Rahmat, Abdallah Flaifel, Benjamin Ferland, Nang K. Su, Michael P. Agius, Jihye Park, Salomon Manier, Mark Bustoros, Daisy Huynh, Marzia Capelletti, Brianna Berrios, Chia Jen Liu, Meng Xiao He, Esteban BraggioRafael Fonseca, Yosef Maruvka, Jennifer L. Guerriero, Melissa Goldman, Eliezer van Allen, Steven A. McCarroll, Jamil Azzi, Gad Getz, Irene M. Ghobrial

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)493-506
Number of pages14
JournalNature Cancer
Volume1
Issue number5
DOIs
StatePublished - May 1 2020

Keywords

  • MGUS
  • SMM
  • immune microenvironment
  • multiple myeloma
  • plasma cells
  • single-cell RNA sequencing
  • tumor microenvironment

ASJC Scopus subject areas

  • Medicine(all)

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