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Identification of Myeloid Derived Suppressor Cells in Tumor Bearing Dogs

Sherger, Matthew George
http://rave.ohiolink.edu/etdc/view?acc_num=osu1337617975

Abstract Details

2012, Master of Science, Ohio State University, Veterinary Clinical Sciences.
For a majority of the past century, cytotoxic chemotherapy has served as the basis for the treatment of cancer, both in humans as well as in domestic animals. While the strategy of using drugs designed primarily to kill rapidly growing neoplastic cells achieved some initial successes, time has proven that this strategy is not sufficient to maintain long-term remissions or cures for most patients. Immunotherapeutic approaches to cancer treatment, such as cancer vaccines, showed initial success in preclinical studies but generally failed to demonstrate the expected clinical activity in patients when evaluated in clinical trials. The shortcomings of such cancer immunotherapies are believed to primarily involve inadequate recruitment of the cellular components of the immune system by the vaccine allowing for poor tumor recognition and subsequent tumor progression and metastasis. One of the pivotal cell types that has been shown to limit the efficacy of these therapies is a cell of bone marrow origin termed a myeloid derived suppressor cells (MDSCs). MDSCs are immature myeloid cells of bone marrow origin that are increased in both cancer bearing mice and humans and distinguished by their co-expression of CD11b and GR-1. Their primary mechanism of action is inhibition of the innate and adaptive T lymphocyte responses. To date these cells have not been described in the dog. The primary limiting factor preventing the identification of these cells in the dog has been a lack of analogous murine, human and canine antibodies. Using commercially available canine antibodies, CD11b and CADO48A, peripheral blood myeloid cells from forty healthy control dogs and forty untreated, tumor-bearing dogs were compared for the differential expression of myeloid cells. Using this technique, a population of CD11blow/CADO48Alow cells was found to be up-regulated in tumor bearing dogs, potentially representing a canine MDSC phenotype. The identification of MDSCs in the canine represents another tool that can be used in better understanding both the biology of cancer as well as the therapeutic opportunities in both the canine and humans.
Tracey Papenfuss, DVM,PhD (Advisor)
William Kisseberth, DVM, PhD (Advisor)
Cheryl London, DVM, PhD (Committee Member)
77 p.
Veterinary Services
cancer immunology; myeloid derived suppressor cells; MDSC

Recommended Citations

Citations

  • Sherger, M. G. (2012). Identification of Myeloid Derived Suppressor Cells in Tumor Bearing Dogs [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1337617975

    APA Style (7th edition)

  • Sherger, Matthew. Identification of Myeloid Derived Suppressor Cells in Tumor Bearing Dogs. 2012. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1337617975.

    MLA Style (8th edition)

  • Sherger, Matthew. "Identification of Myeloid Derived Suppressor Cells in Tumor Bearing Dogs." Master's thesis, Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1337617975

    Chicago Manual of Style (17th edition)

osu1337617975
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© 2012, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.
Release 3.2.12