Analysis of classical neutrophils and polymorphonuclear myeloid-derived suppressor cells in cancer patients and tumor-bearing mice
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-deri...
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| Vydané v: | The Journal of experimental medicine Ročník 218; číslo 4 |
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| Hlavní autori: | , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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United States
05.04.2021
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| ISSN: | 1540-9538, 1540-9538 |
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| 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. |
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| AbstractList | 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. 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.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. |
| Author | Singhal, Sunil Veglia, Filippo Loboda, Andrey Cristescu, Razvan Nam, Brian Patel, Jaymala Sanseviero, Emilio Dweep, Harsh Wilkinson, Patrick Eruslanov, Evgeniy B Sepulveda, Manuel A Nefedova, Yulia Hashimoto, Ayumi De Leo, Alessandra Smirnov, Denis Gabrilovich, Dmitry I Tcyganov, Evgenii Mulligan, Charles Masters, Gregory Kossenkov, Andrew Bhargava, Vipul |
| Author_xml | – sequence: 1 givenname: Filippo surname: Veglia fullname: Veglia, Filippo organization: H. Lee Moffitt Cancer Center, Tampa, FL – sequence: 2 givenname: Ayumi surname: Hashimoto fullname: Hashimoto, Ayumi organization: Wistar Institute, Philadelphia, PA – sequence: 3 givenname: Harsh surname: Dweep fullname: Dweep, Harsh organization: Wistar Institute, Philadelphia, PA – sequence: 4 givenname: Emilio surname: Sanseviero fullname: Sanseviero, Emilio organization: Wistar Institute, Philadelphia, PA – sequence: 5 givenname: Alessandra surname: De Leo fullname: De Leo, Alessandra organization: H. Lee Moffitt Cancer Center, Tampa, FL – sequence: 6 givenname: Evgenii surname: Tcyganov fullname: Tcyganov, Evgenii organization: Wistar Institute, Philadelphia, PA – sequence: 7 givenname: Andrew surname: Kossenkov fullname: Kossenkov, Andrew organization: Wistar Institute, Philadelphia, PA – sequence: 8 givenname: Charles surname: Mulligan fullname: Mulligan, Charles organization: Helen F. Graham Cancer Center and Research Institute, Christiana Care, Newark, DE – sequence: 9 givenname: Brian surname: Nam fullname: Nam, Brian organization: Helen F. Graham Cancer Center and Research Institute, Christiana Care, Newark, DE – sequence: 10 givenname: Gregory surname: Masters fullname: Masters, Gregory organization: Helen F. Graham Cancer Center and Research Institute, Christiana Care, Newark, DE – sequence: 11 givenname: Jaymala surname: Patel fullname: Patel, Jaymala organization: Janssen Research and Development, LLC, Pharmaceutical Companies of Johnson & Johnson, Spring House, PA – sequence: 12 givenname: Vipul surname: Bhargava fullname: Bhargava, Vipul organization: Janssen Research and Development, LLC, Pharmaceutical Companies of Johnson & Johnson, Spring House, PA – sequence: 13 givenname: Patrick surname: Wilkinson fullname: Wilkinson, Patrick organization: Janssen Research and Development, LLC, Pharmaceutical Companies of Johnson & Johnson, Spring House, PA – sequence: 14 givenname: Denis surname: Smirnov fullname: Smirnov, Denis organization: Janssen Research and Development, LLC, Pharmaceutical Companies of Johnson & Johnson, Spring House, PA – sequence: 15 givenname: Manuel A surname: Sepulveda fullname: Sepulveda, Manuel A organization: Janssen Research and Development, LLC, Pharmaceutical Companies of Johnson & Johnson, Spring House, PA – sequence: 16 givenname: Sunil surname: Singhal fullname: Singhal, Sunil organization: Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA – sequence: 17 givenname: Evgeniy B surname: Eruslanov fullname: Eruslanov, Evgeniy B organization: Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA – sequence: 18 givenname: Razvan surname: Cristescu fullname: Cristescu, Razvan organization: Department of Genetics and Pharmacogenomics, Merck Research Laboratories, Merck & Co., Inc., Boston, MA – sequence: 19 givenname: Andrey surname: Loboda fullname: Loboda, Andrey organization: Department of Genetics and Pharmacogenomics, Merck Research Laboratories, Merck & Co., Inc., Boston, MA – sequence: 20 givenname: Yulia surname: Nefedova fullname: Nefedova, Yulia organization: Wistar Institute, Philadelphia, PA – sequence: 21 givenname: Dmitry I surname: Gabrilovich fullname: Gabrilovich, Dmitry I organization: AstraZeneca, Gaithersburg, MD |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33566112$$D View this record in MEDLINE/PubMed |
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