Single-cell RNA sequencing reveals compromised immune microenvironment in precursor stages of multiple myeloma
- 27 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Cancer
- Vol. 1 (5), 493-506
- https://doi.org/10.1038/s43018-020-0053-3
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, monoclonal gammopathy of unknown significance and smoldering MM, to full-blown MM alongside healthy donors, we demonstrate early immune changes during patient progression. We find that natural killer cell abundance is frequently increased in the early stages and associated with altered chemokine receptor expression. As early as smoldering MM, we show loss of granzyme K+ memory cytotoxic T cells and show their critical role in MM immunosurveillance in mouse models. Finally, we report major histocompatibility complex 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 premalignant MM, which will help develop strategies for immune-based patient stratification.Keywords
This publication has 63 references indexed in Scilit:
- Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myelomaLeukemia, 2013
- Critical role for lysyl oxidase in mesenchymal stem cell-driven breast cancer malignancyProceedings of the National Academy of Sciences of the United States of America, 2012
- Coordinated regulation of myeloid cells by tumoursNature Reviews Immunology, 2012
- Harnessing natural killer T (NKT) cells in human myeloma: Progress and challengesClinical Immunology, 2011
- Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective studyBlood, 2009
- Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myelomaBlood, 2008
- Vasculogenic mimicry by bone marrow macrophages in patients with multiple myelomaOncogene, 2007
- Clinical Course and Prognosis of Smoldering (Asymptomatic) Multiple MyelomaThe New England Journal of Medicine, 2007
- Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantationBlood, 2006
- The Hallmarks of CancerCell, 2000