Dataset Information

Identification of myeloid derived suppressor cells in dogs with naturally occurring cancer.

ABSTRACT: Dogs with naturally occurring cancer represent an important large animal model for drug development and testing novel immunotherapies. However, poorly defined immunophenotypes of canine leukocytes have limited the study of tumor immunology in dogs. The accumulation of myeloid derived suppressor cells (MDSCs) is known to be a key mechanism of immune suppression in tumor-bearing mice and in human patients. We sought to identify MDSCs in the blood of dogs with cancer. Peripheral blood mononuclear cells (PBMCs) from dogs with advanced or early stage cancer and from age-matched healthy controls were analyzed by flow cytometry and microscopy. Suppressive function was tested in T cell proliferation and cytokine elaboration assays. Semi-quantitative RT-PCR was used to identify potential mechanisms responsible for immunosuppression. PBMCs from dogs with advanced or metastatic cancer exhibited a significantly higher percentage of CD11b(+)CD14(-)MHCII(-) cells compared to dogs diagnosed with early stage non-metastatic tumors and healthy dogs. These CD11b(+) CD14(-)MHCII(-) cells constitute a subpopulation of activated granulocytes that co-purify with PBMCs, display polymorphonuclear granulocyte morphology, and demonstrate a potent ability to suppress proliferation and IFN-? production in T cells from normal and tumor-bearing donors. Furthermore, these cells expressed hallmark suppressive factors of human MDSC including ARG1, iNOS2, TGF-? and IL-10. In summary our data demonstrate that MDSCs accumulate in the blood of dogs with advanced cancer and can be measured using this three-marker immunophenotype, thereby enabling prospective studies that can monitor MDSC burden.

SUBMITTER: Goulart MR

PROVIDER: S-EPMC3302813 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Identification of myeloid derived suppressor cells in dogs with naturally occurring cancer.

Goulart Michelle R MR Pluhar G Elizabeth GE Ohlfest John R JR

PloS one 20120313 3

Dogs with naturally occurring cancer represent an important large animal model for drug development and testing novel immunotherapies. However, poorly defined immunophenotypes of canine leukocytes have limited the study of tumor immunology in dogs. The accumulation of myeloid derived suppressor cells (MDSCs) is known to be a key mechanism of immune suppression in tumor-bearing mice and in human patients. We sought to identify MDSCs in the blood of dogs with cancer. Peripheral blood mononuclear c ...[more]

PMID: 22428007

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Project description:In periodontitis patients, dysbiosis of the oral microbiota is not only found at clinically diseased periodontal sites but also at clinically healthy periodontal sites, buccal mucosae, tongue, and saliva. The present study evaluated the safety and efficacy of an oral microbiota transplant (OMT) for the treatment of periodontitis in dogs. Eighteen systemically healthy beagle dogs with naturally occurring periodontitis were enrolled in the study and randomly assigned to a test or control group. A 4-y-old, periodontally healthy female beagle dog served as a universal OMT donor. To reduce periodontal inflammation, all dogs received full-mouth mechanical debridement of teeth and mucosae 2 wk before baseline. At baseline, full-mouth mechanical debridement was repeated and followed by adjunctive subgingival and oral irrigation with 0.1% NaOCl. Subsequently, test dogs were inoculated with an OMT from the healthy donor. No daily oral hygiene was performed after OMT transplantation. Adverse events were assessed throughout the observation period. Clinical examinations were performed and whole-mouth oral microbiota samples were collected at week 2, baseline, week 2, and week 12. The composition of oral microbiota samples was analyzed using high-throughput 16S ribosomal RNA gene amplicon sequencing followed by taxonomic assignment and downstream bioinformatic and statistical analyses. Results demonstrated that the intergroup difference in the primary outcome measure, probing pocket depth at week 12, was statistically insignificant. However, the single adjunctive OMT had an additional effect on the oral microbiota composition compared to the full-mouth mechanical and antimicrobial debridement alone. The OMT resulted in an "ecological shift" toward the composition of the donor microbiota, but this was transient in nature and was not observed at week 12. No local or systemic adverse events were observed throughout the study period. The results indicate that OMT may modulate the microbiota composition in dogs with naturally occurring periodontitis and can be applied safely.

Dataset Information

Identification of myeloid derived suppressor cells in dogs with naturally occurring cancer.

Publications

Identification of myeloid derived suppressor cells in dogs with naturally occurring cancer.

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