PMID- 33714729 OWN - NLM STAT- MEDLINE DCOM- 20210910 LR - 20220503 IS - 1090-2163 (Electronic) IS - 0008-8749 (Print) IS - 0008-8749 (Linking) VI - 363 DP - 2021 May TI - Human splenic myeloid derived suppressor cells: Phenotypic and clustering analysis. PG - 104317 LID - S0008-8749(21)00036-8 [pii] LID - 10.1016/j.cellimm.2021.104317 [doi] AB - Myeloid derived suppressor cells (MDSCs) can be subset into monocytic (M-), granulocytic (G-) or polymorphonuclear (PMN-), and immature (i-) or early MDSCs and have a role in many disease states. In cancer patients, the frequencies of MDSCs can positively correlate with stage, grade, and survival. Most clinical studies into MDSCs have been undertaken with peripheral blood (PB); however, in the present studies, we uniquely examined MDSCs in the spleens and PB from patients with gastrointestinal cancers. In our studies, MDSCs were rigorously subset using the following markers: Lineage (LIN) (CD3, CD19 and CD56), human leukocyte antigen (HLA)-DR, CD11b, CD14, CD15, CD33, CD34, CD45, and CD16. We observed a significantly higher frequency of PMN- and M-MDSCs in the PB of cancer patients as compared to their spleens. Expression of the T-cell suppressive enzymes arginase (ARG1) and inducible nitric oxide synthase (i-NOS) were higher on all MDSC subsets for both cancer patients PB and spleen cells as compared to MDSCs from the PB of normal donors. Similar findings for the activation markers lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), program death ligand 1 (PD-L1) and program cell death protein 1 (PD-1) were observed. Interestingly, the total MDSC cell number exported to clustering analyses was similar between all sample types; however, clustering analyses of these MDSCs, using these markers, uniquely documented novel subsets of PMN-, M- and i-MDSCs. In summary, we report a comparison of splenic MDSC frequency, subtypes, and functionality in cancer patients to their PB by clustering and cytometric analyses. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Cole, Kathryn E AU - Cole KE AD - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, United States. FAU - Ly, Quan P AU - Ly QP AD - Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198-4990, United States. FAU - Hollingsworth, Michael A AU - Hollingsworth MA AD - Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, United States. FAU - Cox, Jesse L AU - Cox JL AD - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, United States. FAU - Padussis, James C AU - Padussis JC AD - Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198-4990, United States. FAU - Foster, Jason M AU - Foster JM AD - Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198-4990, United States. FAU - Vargas, Luciano M AU - Vargas LM AD - Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198-4990, United States. FAU - Talmadge, James E AU - Talmadge JE AD - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, United States; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address: jtalmadg@unmc.edu. LA - eng GR - P30 CA036727/CA/NCI NIH HHS/United States GR - P50 CA127297/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20210301 PL - Netherlands TA - Cell Immunol JT - Cellular immunology JID - 1246405 RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - 0 (HLA-DR Antigens) RN - 0 (OLR1 protein, human) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 0 (Scavenger Receptors, Class E) RN - EC 3.5.3.1 (Arginase) SB - IM MH - Adult MH - Aged MH - Arginase/metabolism MH - B7-H1 Antigen/metabolism MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - Cluster Analysis MH - Female MH - Flow Cytometry/methods MH - Gastrointestinal Neoplasms/immunology MH - HLA-DR Antigens/metabolism MH - Humans MH - Male MH - Middle Aged MH - Myeloid-Derived Suppressor Cells/cytology/immunology/*metabolism MH - Neoplasms/immunology MH - Programmed Cell Death 1 Receptor/metabolism MH - Scavenger Receptors, Class E/metabolism MH - Spleen/*immunology/pathology PMC - PMC8077751 MID - NIHMS1683116 OTO - NOTNLM OT - Cancer patient peripheral blood OT - Cancer patient spleen OT - Flow cytometry OT - MDSC OT - SPADE EDAT- 2021/03/15 06:00 MHDA- 2021/09/11 06:00 PMCR- 2022/05/01 CRDT- 2021/03/14 20:41 PHST- 2020/11/17 00:00 [received] PHST- 2021/02/11 00:00 [revised] PHST- 2021/02/12 00:00 [accepted] PHST- 2021/03/15 06:00 [pubmed] PHST- 2021/09/11 06:00 [medline] PHST- 2021/03/14 20:41 [entrez] PHST- 2022/05/01 00:00 [pmc-release] AID - S0008-8749(21)00036-8 [pii] AID - 10.1016/j.cellimm.2021.104317 [doi] PST - ppublish SO - Cell Immunol. 2021 May;363:104317. doi: 10.1016/j.cellimm.2021.104317. Epub 2021 Mar 1.