[Multibilly]

Interesting study re: MGUS & smoldering myeloma

by Multibilly on Wed Sep 23, 2020 6:16 pm

I found this research especially interesting since the changes in the patient's immune micro­en­vironment didn't correlate with other precursor conditions (which I assume were the conditions spelled out in the current diagnostic criteria for MGUS, smoldering myeloma, and multiple myeloma):

Zavidij, O., Haradhvala, N.J., Mouhieddine, T.H. et al., "Single-cell RNA sequencing reveals compromised immune microenvironment in precursor stages of multiple myeloma," Nature Cancer, April 27, 2020.

Abstract:

Precursor states of mul­ti­ple myeloma 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 multiple myeloma, to full-blown multiple myeloma 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 multiple myeloma, we show loss of granzyme K+ memory cyto­toxic T cells and show their crit­i­cal role in multiple myeloma 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 multiple myeloma, which will help de­vel­op strategies for im­mune-based patient stratification.