Single-cell analysis reveals favorable responses of tumor-associated monocytes to bortezomib-based treatment in multiple myeloma.

Abstract

The bone marrow microenvironment (BME) has a significant effect on bortezomib (BTZ)-based chemotherapy in patients with multiple myeloma (MM). However, how BME components drive effective BTZ-based chemotherapy to facilitate antitumor responses has yet to be fully understood. Using single-cell transcriptome analysis, we discerned a notable increase in the density of tumor-associated IL1B⁺ monocytes (TAMO_IL1B), a CD14⁺ monocyte subcluster, within the optimal responders (OR) group compared with the suboptimal responders (SOR) group. TAMO_IL1B in the OR group had significantly greater effects on the TGF-β signaling pathway. The ligand-receptor pair (THBS1-SDC1) interaction intensity in the THBS1 signaling pathway between TAMO_IL1B and tumor plasma cells (TPC) in the OR group was significantly greater than that in the SOR group. Furthermore, pseudotime trajectory analysis indicated that TAMO_IL1B predominantly occupied late differentiation stages and was associated with a favorable response within the OR group. These findings reveal a previously unrecognized role for TAMO_IL1B in shaping antitumor immunity. The THBS1-SDC1 axis may contribute to interactions between monocytes and plasma cells; however, functional validation is required before any therapeutic implications can be drawn.