期刊论文详细信息
BMC Veterinary Research
Identification of myeloid derived suppressor cells in the peripheral blood of tumor bearing dogs
Tracey L Papenfuss2  Susan Olivo-Marston3  Cheryl London1  William Kisseberth1  Matthew Sherger1 
[1] Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH, USA;Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH, USA;Division of Epidemiology, College of Public Health, The Ohio State University, 1841 Neil Avenue, Columbus, OH, USA
关键词: Immunosuppression;    Cancer immunotherapy;    Myeloid derived suppressor cells;   
Others  :  1119678
DOI  :  10.1186/1746-6148-8-209
 received in 2012-05-22, accepted in 2012-10-24,  发布年份 2012
PDF
【 摘 要 】

Background

Myeloid derived suppressor cells (MDSCs) are a recently described population of immune cells that significantly contribute to the immunosuppression seen in cancer patients. MDSCs are one of the most important factors that limit the efficacy of cancer immunotherapy (e.g. cancer vaccines) and MDSC levels are increased in cancer in multiple species. Identifying and targeting MDSCs is actively being investigated in the field of human oncology and is increasingly being investigated in veterinary oncology. The treatment of canine cancer not only benefits dogs, but is being used for translational studies evaluating and modifcying candidate therapies for use in humans. Thus, it is necessary to understand the immune alterations seen in canine cancer patients which, to date, have been relatively limited. This study investigates the use of commercially available canine antibodies to detect an immunosuppressive (CD11blow/CADO48low) cell population that is increased in the peripheral blood of tumor-bearing dogs.

Results

Commercially available canine antibodies CD11b and CADO48A were used to evaluate white blood cells from the peripheral blood cells of forty healthy control dogs and forty untreated, tumor-bearing dogs. Tumor-bearing dogs had a statistically significant increase in CD11blow/CADO48Alow cells (7.9%) as compared to the control dogs (3.6%). Additionally, sorted CD11blow/CADO48Alow generated in vitro suppressed the proliferation of canine lymphocytes.

Conclusions

The purpose of this study was aimed at identifying potential canine specific markers for identifying MDSCs in the peripheral blood circulation of dogs. This study demonstrates an increase in a unique CD11blow/CADO48Alow cell population in tumor-bearing dogs. This immunophenotype is consistent with described phenotypes of MDSCs in other species (i.e. mice) and utilizes commercially available canine-specific antibodies. Importantly, CD11blow/CADO48Alow from a tumor environment suppress the proliferation of lymphocytes. These results provide a useful phenotype of cells increased in canine cancer patients that may serve as a useful prognostic marker for assessing immune status and functional response to cancer immunotherapies in dogs. Understanding MDSCs in dogs will allow for increased effectiveness of cancer immunotherapy in both dogs and humans.

【 授权许可】

   
2012 Sherger et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150208100343818.pdf 3018KB PDF download
Figure 7. 38KB Image download
Figure 6. 110KB Image download
Figure 5. 40KB Image download
Figure 4. 79KB Image download
Figure 3. 87KB Image download
Figure 2. 84KB Image download
Figure 1. 49KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】
  • [1]Gabrilovich DI, Nagaraj S: Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009, 9(3):162-174.
  • [2]Youn JI, Gabrilovich DI: The biology of myeloid-derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity. Eur J Immunol 2010, 40(11):2969-2975.
  • [3]Medzhitov R, et al.: Highlights of 10 years of immunology in Nature Reviews Immunology. Nat Rev Immunol 2011, 11(10):693-702.
  • [4]Krystal G, et al.: Re: the terminology issue for myeloid-derived suppressor cells. Cancer Res 2007, 67(8):3986.
  • [5]Kirchner H, et al.: Evidence of suppressor cell activity in spleens of mice bearing primary tumors induced by Moloney sarcoma virus. J Exp Med 1974, 139(6):1473-1487.
  • [6]Gabrilovich DI, et al.: Dendritic cells in antitumor immune responses. II. Dendritic cells grown from bone marrow precursors, but not mature DC from tumor-bearing mice, are effective antigen carriers in the therapy of established tumors. Cell Immunol 1996, 170(1):111-119.
  • [7]Diaz-Montero CM, et al.: Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 2009, 58(1):49-59.
  • [8]Ko JS, et al.: Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res 2009, 15(6):2148-2157.
  • [9]London CA: Tyrosine kinase inhibitors in veterinary medicine. Top Companion Anim Med 2009, 24(3):106-112.
  • [10]Ugel S, et al.: Therapeutic targeting of myeloid-derived suppressor cells. Curr Opin Pharmacol 2009, 9(4):470-481.
  • [11]Serafini P, Borrello I, Bronte V: Myeloid suppressor cells in cancer: recruitment, phenotype, properties, and mechanisms of immune suppression. Semin Cancer Biol 2006, 16(1):53-65.
  • [12]Shojaei F, et al.: Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol 2007, 25(8):911-920.
  • [13]Fujita M, et al.: COX-2 blockade suppresses gliomagenesis by inhibiting myeloid-derived suppressor cells. Cancer Res 2011, 71(7):2664-2674.
  • [14]Bunt SK, et al.: Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression. Cancer Res 2007, 67(20):10019-10026.
  • [15]Ilkovitch D, Lopez DM: The liver is a site for tumor-induced myeloid-derived suppressor cell accumulation and immunosuppression. Cancer Res 2009, 69(13):5514-5521.
  • [16]Talmadge JE: Pathways mediating the expansion and immunosuppressive activity of myeloid-derived suppressor cells and their relevance to cancer therapy. Clin Cancer Res 2007, 13(18 Pt 1):5243-5248.
  • [17]Pan PY, et al.: Immune stimulatory receptor CD40 is required for T-cell suppression and T regulatory cell activation mediated by myeloid-derived suppressor cells in cancer. Cancer Res 2010, 70(1):99-108.
  • [18]Ostrand-Rosenberg S: Myeloid-derived suppressor cells: more mechanisms for inhibiting antitumor immunity. Cancer Immunol Immunother 2010, 59(10):1593-1600.
  • [19]Ostrand-Rosenberg S, Sinha P: Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 2009, 182(8):4499-4506.
  • [20]Bergman PJ, et al.: Development of a xenogeneic DNA vaccine program for canine malignant melanoma at the Animal Medical Center. Vaccine 2006, 24(21):4582-4585.
  • [21]Goulart MR, Pluhar GE, Ohlfest JR: Identification of myeloid derived suppressor cells in dogs with naturally occurring cancer. PLoS One 2012, 7(3):e33274.
  • [22]Mitchell L, Thamm DH, Biller BJ: Clinical and immunomodulatory effects of toceranib combined with low-dose cyclophosphamide in dogs with cancer. J Vet Intern Med 2012, 26(2):355-362.
  • [23]Kobayashi T, et al.: Canine hair-follicle keratinocytes enriched with bulge cells have the highly proliferative characteristic of stem cells. Vet Dermatol 2009, 20(5–6):338-346.
  • [24]Mazzone A, et al.: Correlation between CD11b/CD18 and increase of aggregability of granulocytes in coronary artery disease. Inflammation 1992, 16(4):315-323.
  • [25]Lin TY, Rush LJ, London CA: Generation and characterization of bone marrow-derived cultured canine mast cells. Vet Immunol Immunopathol 2006, 113(1–2):37-52.
  • [26]Pinet F, et al.: Morphology, homogeneity and functionality of human monocytes-derived macrophages. Cell Mol Biol (Noisy-le-grand) 2003, 49(6):899-905.
  • [27]Schuberth HJ, et al.: Reactivity of cross-reacting monoclonal antibodies with canine leukocytes, platelets and erythrocytes. Vet Immunol Immunopathol 2007, 119(1–2):47-55.
  • [28]Rebuck N, Finn A: Polymorphonuclear granulocyte expression of CD11a/CD18, CD11b/CD18 and L-selectin in normal individuals. FEMS Immunol Med Microbiol 1994, 8(3):189-195.
  • [29]Dosogne H, et al.: Increased surface expression of CD11b receptors on polymorphonuclear leukocytes is not sufficient to sustain phagocytosis during Escherichia coli mastitis in early postpartum dairy cows. Vet Immunol Immunopathol 1997, 60(1–2):47-59.
  • [30]Chang HH, et al.: Multistable and multistep dynamics in neutrophil differentiation. BMC Cell Biol 2006, 7:11. BioMed Central Full Text
  • [31]Furuhashi K, et al.: Mouse lung CD103+ and CD11bhigh dendritic cells preferentially induce distinct CD4+ T-cell responses. Am J Respir Cell Mol Biol 2012, 46(2):165-172.
  • [32]Porembka MR, et al.: Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid-derived suppressor cells which promote primary tumor growth. Cancer Immunol Immunother 2012.
  • [33]Zhao F, et al.: S100A9 a new marker for monocytic human myeloid derived suppressor cells. Immunology 2012.
  • [34]Ryzhov S, et al.: Adenosinergic regulation of the expansion and immunosuppressive activity of CD11b+Gr1+ cells. J Immunol 2011, 187(11):6120-6129.
  • [35]Greten TF, Manns MP, Korangy F: Myeloid derived suppressor cells in human diseases. Int Immunopharmacol 2011, 11(7):802-807.
  • [36]Raychaudhuri B, et al.: Myeloid-derived suppressor cell accumulation and function in patients with newly diagnosed glioblastoma. Neuro Oncol 2011, 13(6):591-599.
  文献评价指标  
  下载次数:38次 浏览次数:1次