CD115− monocytic myeloid-derived suppressor cells are precursors of OLFM4high polymorphonuclear myeloid-derived suppressor cells

Author:

Zou YunyunORCID,Kamada Nobuhiko,Seong Seung-YongORCID,Seo Sang-UkORCID

Abstract

AbstractMyeloid-derived suppressor cells (MDSCs) consist of monocytic (M-) MDSCs and polymorphonuclear (PMN-) MDSCs that contribute to an immunosuppressive environment in tumor-bearing hosts. However, research on the phenotypic and functional heterogeneity of MDSCs in tumor-bearing hosts and across different disease stage is limited. Here we subdivide M-MDSCs based on CD115 expression and report that CD115 M-MDSCs are functionally distinct from CD115+ M-MDSCs. CD115 M-MDSCs increased in bone marrow and blood as tumors progressed. Transcriptome analysis revealed that CD115 M-MDSCs expressed higher levels of neutrophil-related genes. Moreover, isolated CD115 M-MDSCs had higher potential to be differentiated into PMN-MDSCs compared with CD115+ M-MDSCs. Of note, CD115 M-MDSCs were able to differentiate into both olfactomedin 4 (OLFM4)hi and OLFM4lo PMN-MDSCs, whereas CD115+ M-MDSCs differentiated into a smaller proportion of OLFM4lo PMN-MDSCs. In vivo, M-MDSC to PMN-MDSC differentiation occurred most frequently in bone marrow while M-MDSCs preferentially differentiated into tumor-associated macrophages in the tumor mass. Our study reveals the presence of previously unrecognized subtypes of CD115 M-MDSCs in tumor-bearing hosts and demonstrates their cellular plasticity during tumorigenesis.

Funder

National Research Foundation of Korea

Publisher

Springer Science and Business Media LLC

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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