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Analysis of classical neutrophils and polymorphonuclear myeloid-derived suppressor cells in cancer patients and tumor-bearing mice.

ABSTRACT: In this study, using single-cell RNA-seq, cell mass spectrometry, flow cytometry, and functional analysis, we characterized the heterogeneity of polymorphonuclear neutrophils (PMNs) in cancer. We describe three populations of PMNs in tumor-bearing mice: classical PMNs, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and activated PMN-MDSCs with potent immune suppressive activity. In spleens of mice, PMN-MDSCs gradually replaced PMNs during tumor progression. Activated PMN-MDSCs were found only in tumors, where they were present at the very early stages of the disease. These populations of PMNs in mice could be separated based on the expression of CD14. In peripheral blood of cancer patients, we identified two distinct populations of PMNs with characteristics of classical PMNs and PMN-MDSCs. The gene signature of tumor PMN-MDSCs was similar to that in mouse activated PMN-MDSCs and was closely associated with negative clinical outcome in cancer patients. Thus, we provide evidence that PMN-MDSCs are a distinct population of PMNs with unique features and potential for selective targeting opportunities.

SUBMITTER: Veglia F

PROVIDER: S-EPMC7879582 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Analysis of classical neutrophils and polymorphonuclear myeloid-derived suppressor cells in cancer patients and tumor-bearing mice.

Veglia Filippo F Hashimoto Ayumi A Dweep Harsh H Sanseviero Emilio E De Leo Alessandra A Tcyganov Evgenii E Kossenkov Andrew A Mulligan Charles C Nam Brian B Masters Gregory G Patel Jaymala J Bhargava Vipul V Wilkinson Patrick P Smirnov Denis D Sepulveda Manuel A MA Singhal Sunil S Eruslanov Evgeniy B EB Cristescu Razvan R Loboda Andrey A Nefedova Yulia Y Gabrilovich Dmitry I DI

The Journal of experimental medicine 20210401 4

In this study, using single-cell RNA-seq, cell mass spectrometry, flow cytometry, and functional analysis, we characterized the heterogeneity of polymorphonuclear neutrophils (PMNs) in cancer. We describe three populations of PMNs in tumor-bearing mice: classical PMNs, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and activated PMN-MDSCs with potent immune suppressive activity. In spleens of mice, PMN-MDSCs gradually replaced PMNs during tumor progression. Activated PMN-MDSCs w ...[more]

PMID: 33566112

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Project description:Background Immune cells play a vital role in the pathology of ischemic stroke. Neutrophils and polymorphonuclear myeloid-derived suppressor cells share a similar phenotype and have attracted increasing attention in immune regulation research, yet their dynamics in ischemic stroke remain elusive. Methods and Results Mice were randomly divided into 2 groups and intraperitoneally treated with anti-Ly6G (lymphocyte antigen 6 complex locus G) monoclonal antibody or saline. Distal middle cerebral artery occlusion and transient middle cerebral artery occlusion were applied to induce experimental stroke, and mice mortality was recorded until 28 days after stroke. Green fluorescent nissl staining was used to measure infarct volume. Cylinder and foot fault tests were used to evaluate neurological deficits. Immunofluorescence staining was conducted to confirm Ly6G neutralization and detect activated neutrophils and CD11b+Ly6G+ cells. Fluorescence-activated cell sorting was performed to evaluate polymorphonuclear myeloid-derived suppressor cell accumulation in brains and spleens after stroke. Anti-Ly6G antibody successfully depleted Ly6G expression in mice cortex but did not alter cortical physiological vasculature. Prophylactic anti-Ly6G antibody treatment ameliorated ischemic stroke outcomes in the subacute phase. Moreover, using immunofluorescence staining, we found that anti-Ly6G antibody suppressed activated neutrophil infiltration into parenchyma and decreased neutrophil extracellular trap formation in penumbra after stroke. Additionally, prophylactic anti-Ly6G antibody treatment reduced polymorphonuclear myeloid-derived suppressor cell accumulation in the ischemic hemisphere. Conclusions Our study suggested a protective effect of prophylactic anti-Ly6G antibody administration against ischemic stroke by reducing activated neutrophil infiltration and neutrophil extracellular trap formation in parenchyma and suppressing polymorphonuclear myeloid-derived suppressor cell accumulation in the brain. This study may provide a novel therapeutic approach for ischemic stroke.

Dataset Information

Analysis of classical neutrophils and polymorphonuclear myeloid-derived suppressor cells in cancer patients and tumor-bearing mice.

Publications

Analysis of classical neutrophils and polymorphonuclear myeloid-derived suppressor cells in cancer patients and tumor-bearing mice.

Similar Datasets

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