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Mass cytometry discovers two discrete subsets of CD39-Treg which discriminate MGUS from Multiple Myeloma

Marsh-Wakefield, F., Kruzins, A., McGuire, H.M. et al.

Multiple Myeloma (MM) is preceded by the clinically stable condition monoclonal gammopathy of undetermined significance (MGUS), which is defined by the presence of a monoclonal protein and less than 10% malignant plasma cell infiltration in the bone marrow (BM). Critical immune events that discriminate MGUS from newly diagnosed MM (NDMM) patients remain unknown, but may involve changes in the regulatory T cell (Treg) compartment that favour myeloma growth. To address this possibility, we used mass cytometry to interrogate the distribution of multiple subsets within CD25+CD27low/negTreg in matched BM and peripheral blood (PB) of MGUS and NDMM patients. Both mass cytometry and flow cytometry confirmed a dominance of CD39-Treg within the Treg compartment in BM and PB of NDMM patients compared to an even distribution of CD39-Treg and CD39+Treg in MGUS patients. Unsupervised clustering displayed a phenotypic organisation of Treg into 25 metaclusters that confirmed Treg heterogeneity and identified two subsets which emerged exclusively within CD39-Treg of NDMM patients. One subset was found in both BM and PB that phenotypically resembled activated Treg based on CD45RO, CD49d, and CD62L expression; another subset resembled BM-resident Treg based on its tissue-resident phenotype characterised by CD69 expression, a lack of CD62L and CD49d expression and restricted location within the BM. PD-1 and TIGIT coexpressed on activated Treg, while PD-1 was expressed at higher levels on BM-resident Treg then on activated Treg. Both subsets produce Perforin and Granzyme B. In conclusion, the use of mass cytometry discovered two discrete subsets of CD39-Treg which may be permissive of myeloma growth. Understanding the regulatory properties of these subsets may also advance MGUS and MM diagnosis, prognosis, and therapeutic implications for MM patients.

Citation

Marsh-Wakefield, F., Kruzins, A., McGuire, H.M. et al. "Mass cytometry discovers two discrete subsets of CD39-Treg which discriminate MGUS from Multiple Myeloma" Frontiers in Immunology (2019): doi: 10.3389/fimmu.2019.01596