PMID- 31446208
OWN - NLM
STAT- MEDLINE
DCOM- 20191126
LR  - 20191126
IS  - 1873-2534 (Electronic)
IS  - 0165-2427 (Linking)
VI  - 216
DP  - 2019 Oct
TI  - Characterization of myeloid-derived suppressor cells and cytokines GM-CSF, IL-10 
      and MCP-1 in dogs with malignant melanoma receiving a GD3-based immunotherapy.
PG  - 109912
LID - S0165-2427(19)30050-9 [pii]
LID - 10.1016/j.vetimm.2019.109912 [doi]
AB  - Melanoma in humans and canines is an aggressive and highly metastatic cancer. The 
      mucosal forms in both species share genetic and histopathologic features, making 
      dogs a valuable spontaneous disease animal model. Myeloid-derived suppressor 
      cells (MDSCs) are a heterogeneous population of cells of myeloid origin with 
      immunosuppressive capabilities, which are increased in many human cancers and 
      contribute to tumor immune evasion. They are a possible target to improve 
      immunotherapy outcomes. Current information regarding MDSCs in canines is 
      minimal, limiting their use as translational model for the study of MDSCs. The 
      objective of this study was to characterize major MDSCs subsets (monocytic and 
      polymorphonuclear) and the cytokines granulocyte-macrophage colony-stimulating 
      factor (GM-CSF), interleukin 10 (IL-10) and monocyte chemoattractant protein-1 
      (MCP-1) in canines with malignant melanoma and to evaluate changes in MDSCs and 
      the cytokines over time in response to a GD3-based active immunotherapy. Whole 
      blood and serum collected from 30 healthy controls and 33 patients enrolled in 
      the University of Florida melanoma vaccine trial were analyzed by flow cytometry 
      with canine specific CD11b, MHCII and anti-human CD14 antibodies to assess 
      ostensibly polymorphonuclear-MDSC (CD11b(+) MHCII(-) CD14(-)) and monocytic-MDSC 
      (CD11b(+) MHCII(-) CD14(+)) subsets. IL-10, MCP-1 and both MDSCs subsets were 
      significantly elevated in melanoma dogs versus controls. Both MDSCs subsets 
      decreased significantly following GD3-based immunotherapy administration but no 
      significant changes in cytokines were seen over time. To our knowledge, this is 
      the first report documenting increased monocytic-MDSCs in canine melanoma. This 
      is consistent with human malignant melanoma data, supporting dogs as a valuable 
      model for therapeutic intervention studies.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Hutchison, S
AU  - Hutchison S
AD  - Department of Small Animal Clinical Sciences, University of Florida, Gainesville, 
      FL, USA.
FAU - Sahay, B
AU  - Sahay B
AD  - Department of Infectious Disease and Immunology, University of Florida, 
      Gainesville, FL, USA.
FAU - de Mello, Souza Ch
AU  - de Mello SC
AD  - Department of Small Animal Clinical Sciences, University of Florida, Gainesville, 
      FL, USA.
FAU - Sayour, E J
AU  - Sayour EJ
AD  - Preston A. Wells, Jr. Center for Brain Tumor Therapy, University of Florida Brain 
      Tumor Immunotherapy Program, McKnight Brain Institute, Department of 
      Neurosurgery, University of Florida, Gainesville, FL, USA.
FAU - Lejeune, A
AU  - Lejeune A
AD  - Department of Small Animal Clinical Sciences, University of Florida, Gainesville, 
      FL, USA.
FAU - Szivek, A
AU  - Szivek A
AD  - Department of Small Animal Clinical Sciences, University of Florida, Gainesville, 
      FL, USA.
FAU - Livaccari, A M
AU  - Livaccari AM
AD  - Department of Small Animal Clinical Sciences, University of Florida, Gainesville, 
      FL, USA.
FAU - Fox-Alvarez, S
AU  - Fox-Alvarez S
AD  - Department of Small Animal Clinical Sciences, University of Florida, Gainesville, 
      FL, USA.
FAU - Salute, M
AU  - Salute M
AD  - Department of Small Animal Clinical Sciences, University of Florida, Gainesville, 
      FL, USA.
FAU - Powers, L
AU  - Powers L
AD  - Department of Small Animal Clinical Sciences, University of Florida, Gainesville, 
      FL, USA.
FAU - Milner, R J
AU  - Milner RJ
AD  - Department of Small Animal Clinical Sciences, University of Florida, Gainesville, 
      FL, USA. Electronic address: milnerr@ufl.edu.
LA  - eng
PT  - Clinical Trial, Veterinary
PT  - Journal Article
DEP - 20190731
PL  - Netherlands
TA  - Vet Immunol Immunopathol
JT  - Veterinary immunology and immunopathology
JID - 8002006
RN  - 0 (Chemokine CCL2)
RN  - 0 (Gangliosides)
RN  - 0 (sialogangliosides)
RN  - 130068-27-8 (Interleukin-10)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Dog Diseases/metabolism/*therapy
MH  - Dogs
MH  - Female
MH  - Gangliosides/administration & dosage/therapeutic use
MH  - Gene Expression Regulation/drug effects
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/genetics/*metabolism
MH  - Immunotherapy
MH  - Interleukin-10/genetics/*metabolism
MH  - Male
MH  - Melanoma/therapy/*veterinary
MH  - Myeloid-Derived Suppressor Cells/*physiology
OTO - NOTNLM
OT  - Chemokines
OT  - Cytokines
OT  - Immunotherapy
OT  - Melanoma
OT  - Myeloid-derived suppressor cells (MDSCs)
OT  - dog/canine
EDAT- 2019/08/26 06:00
MHDA- 2019/11/27 06:00
CRDT- 2019/08/26 06:00
PHST- 2019/02/14 00:00 [received]
PHST- 2019/07/23 00:00 [revised]
PHST- 2019/07/30 00:00 [accepted]
PHST- 2019/08/26 06:00 [pubmed]
PHST- 2019/11/27 06:00 [medline]
PHST- 2019/08/26 06:00 [entrez]
AID - S0165-2427(19)30050-9 [pii]
AID - 10.1016/j.vetimm.2019.109912 [doi]
PST - ppublish
SO  - Vet Immunol Immunopathol. 2019 Oct;216:109912. doi: 10.1016/j.vetimm.2019.109912. 
      Epub 2019 Jul 31.