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

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. We employed single-cell RNA sequencing on 40.8K immune microenvironmental cells using 32 bone marrow samples from a cohort of 22 patients with varying stages of Multiple Myeloma progression and 9 healthy donors. >>>Submitter states that raw data will be submitted to dbGaP due to patient privacy concerns<<<