| Literature DB >> 33409501 |
Oksana Zavidij1,2,3, Nicholas J Haradhvala3,4,5, Tarek H Mouhieddine1,2,3, Romanos Sklavenitis-Pistofidis1,2,3, Songjie Cai2,6, Mairead Reidy1,2,3, Mahshid Rahmat1,2,3, Abdallah Flaifel2,7, Benjamin Ferland7, Nang K Su1, Michael P Agius1,2,3, Jihye Park1,2,3, Salomon Manier1,2, Mark Bustoros1,2,3, Daisy Huynh1, Marzia Capelletti1,2,3, Brianna Berrios1, Chia-Jen Liu1,2, Meng Xiao He3,5, Esteban Braggio8, Rafael Fonseca8, Yosef E Maruvka3, Jennifer L Guerriero1,2, Melissa Goldman2,3, Eliezer M Van Allen1,2,3, Steven A McCarroll2,3, Jamil Azzi2,6, Gad Getz9,10,11, Irene M Ghobrial12,13,14.
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.Entities:
Keywords: MGUS; SMM; immune microenvironment; multiple myeloma; plasma cells; single-cell RNA sequencing; tumor microenvironment
Mesh：
Year: 2020 PMID： 33409501 PMCID： PMC7785110 DOI： 10.1038/s43018-020-0053-3
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347