TY - JOUR
T1 - Single-cell RNA sequencing reveals compromised immune microenvironment in precursor stages of multiple myeloma
AU - Zavidij, Oksana
AU - Haradhvala, Nicholas J.
AU - Mouhieddine, Tarek H.
AU - Sklavenitis-Pistofidis, Romanos
AU - Cai, Songjie
AU - Reidy, Mairead
AU - Rahmat, Mahshid
AU - Flaifel, Abdallah
AU - Ferland, Benjamin
AU - Su, Nang K.
AU - Agius, Michael P.
AU - Park, Jihye
AU - Manier, Salomon
AU - Bustoros, Mark
AU - Huynh, Daisy
AU - Capelletti, Marzia
AU - Berrios, Brianna
AU - Liu, Chia Jen
AU - He, Meng Xiao
AU - Braggio, Esteban
AU - Fonseca, Rafael
AU - Maruvka, Yosef
AU - Guerriero, Jennifer L.
AU - Goldman, Melissa
AU - van Allen, Eliezer
AU - McCarroll, Steven A.
AU - Azzi, Jamil
AU - Getz, Gad
AU - Ghobrial, Irene M.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
KW - MGUS
KW - SMM
KW - immune microenvironment
KW - multiple myeloma
KW - plasma cells
KW - single-cell RNA sequencing
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85086913202&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086913202&partnerID=8YFLogxK
U2 - 10.1038/s43018-020-0053-3
DO - 10.1038/s43018-020-0053-3
M3 - Article
C2 - 33409501
AN - SCOPUS:85086913202
SN - 2662-1347
VL - 1
SP - 493
EP - 506
JO - Nature Cancer
JF - Nature Cancer
IS - 5
ER -