Skip to main content

Advertisement

Springer Nature Link
Log in

Myeloid-derived suppressor cells in mammary tumor progression in FVB Neu transgenic mice

  • Original Article
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Female mice transgenic for the rat proto-oncogene c-erb-B2, under control of the mouse mammary tumor virus (MMTV) promoter (neuN), spontaneously develop metastatic mammary carcinomas. The development of these mammary tumors is associated with increased number of GR-1+CD11b+ myeloid derived suppressor cells (MDSCs) in the peripheral blood (PB), spleen and tumor. We report a complex relationship between tumor growth, MDSCs and immune regulatory molecules in non-mutated neu transgenic mice on a FVB background (FVB-neuN). The first and second tumors in FVB-neuN mice develop at a median of 265 (147–579) and 329 (161–523) days, respectively, resulting in a median survival time (MST) of 432 (201 to >500) days. During tumor growth, significantly increased number of MDSCs is observed in the PB and spleen, as well as, in infiltrating the mammary tumors. Our results demonstrate a direct correlation between tumor size and the number of MDSCs infiltrating the tumor and an inverse relationship between the frequency of CD4+ T-cells and MDSCs in the spleen. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assessment of enzyme and cytokine transcript levels in the spleen, tumor, tumor-infiltrating non-parenchymal cells (NPCs) and mammary glands revealed a significant increase in transcript levels from grossly normal mammary glands and tumor-infiltrating NPCs during tumor progression. Tumor NPCs, as compared to spleen cells from wild-type (w/t) mice, expressed significantly higher levels of arginase-1 (ARG-1), nitric oxide synthase (NOS-2), vascular endothelial growth factor (VEGF-A) and significantly lower levels of interferon (IFN)-γ, interleukin (IL)-2 and fms-like tyrosine kinase-3 ligand (Flt3L) transcript levels. Transcript levels in the spleens of tumor-bearing (TB) mice also differed from normal mice, although to a lesser extent than transcript levels from tumor-infiltrating NPCs. Furthermore, both spleen cells and NPCs from TB mice, but not control mice, suppressed alloantigen responses by syngeneic control spleen cells. Correlative studies revealed that the number of MDSCs in the spleen was directly associated with granulocyte colony stimulating factor (G-CSF) transcript levels in the spleen; while the number of MDSCs in the tumors was directly correlated with splenic granulocyte macrophage stimulating factor (GM-CSF) transcript levels, tumor volume and tumor cell number. Together our results support a role for MDSCs in tumor initiation and progressive, T-cell depression and loss of function provide evidence which support multiple mechanisms of MDSC expansion in a site-dependent manner.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Kaplan RN, Psaila B, Lyden D (2006) Bone marrow cells in the ‘pre-metastatic niche’: within bone and beyond. Cancer Metastasis Rev 25(4):521–529

    Article  PubMed  Google Scholar 

  2. Ahn GO, Brown JM (2008) Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells. Cancer Cell 13(3):193–205

    Article  PubMed  CAS  Google Scholar 

  3. Seandel M, Butler J, Lyden D, Rafii S (2008) A catalytic role for proangiogenic marrow-derived cells in tumor neovascularization. Cancer Cell 13(3):181–183

    Article  PubMed  CAS  Google Scholar 

  4. Fricke I, Mirza N, Dupont J, Lockhart C, Jackson A, Lee JH et al (2007) Vascular endothelial growth factor-trap overcomes defects in dendritic cell differentiation but does not improve antigen-specific immune responses. Clin Cancer Res 13(16):4840–4848

    Article  PubMed  CAS  Google Scholar 

  5. Serafini P, Meckel K, Kelso M, Noonan K, Califano J, Koch W et al (2006) Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med 203(12):2691–2702

    Article  PubMed  CAS  Google Scholar 

  6. Serafini P, Mgebroff S, Noonan K, Borrello I (2008) Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res 68(13):5439–5449

    Article  PubMed  CAS  Google Scholar 

  7. Melani C, Chiodoni C, Forni G, Colombo MP (2003) Myeloid cell expansion elicited by the progression of spontaneous mammary carcinomas in c-erbB-2 transgenic BALB/c mice suppresses immune reactivity. Blood 102(6):2138–2145

    Article  PubMed  CAS  Google Scholar 

  8. Bronte V, Serafini P, Apolloni E, Zanovello P (2001) Tumor-induced immune dysfunctions caused by myeloid suppressor cells. J Immunother 24(6):431–446

    Article  PubMed  CAS  Google Scholar 

  9. Grizzle WE, Xu X, Zhang S, Stockard CR, Liu C, Yu S et al (2007) Age-related increase of tumor susceptibility is associated with myeloid-derived suppressor cell mediated suppression of T cell cytotoxicity in recombinant inbred BXD12 mice. Mech Ageing Dev 128(11–12):672–680

    Article  PubMed  CAS  Google Scholar 

  10. Talmadge JE (2007) Pathways mediating the expansion and immunosuppressive activity of myeloid-derived suppressor cells and their relevance to cancer therapy. Clin Cancer Res 13(18 Pt 1):5243–5248

    Article  PubMed  CAS  Google Scholar 

  11. Gabrilovich D (2004) Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat Rev Immunol 4(12):941–952

    Article  PubMed  CAS  Google Scholar 

  12. Badger AM, King AG, Talmadge JE, Schwartz DA, Picker DH, Mirabelli CK et al (1990) Induction of non-specific suppressor cells in normal Lewis rats by a novel azaspirane SK&F 105685. J Autoimmun 3(4):485–500

    Article  PubMed  CAS  Google Scholar 

  13. Holda JH, Maier T, Claman HN (1985) Murine graft-versus-host disease across minor barriers: immunosuppressive aspects of natural suppressor cells. Immunol Rev 88:87–105

    Article  PubMed  CAS  Google Scholar 

  14. Strober S (1984) Natural suppressor (NS) cells, neonatal tolerance, and total lymphoid irradiation: exploring obscure relationships. Annu Rev Immunol 2:219–237

    Article  PubMed  CAS  Google Scholar 

  15. Bronte V, Apolloni E, Cabrelle A, Ronca R, Serafini P, Zamboni P et al (2000) Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. Blood 96(12):3838–3846

    PubMed  CAS  Google Scholar 

  16. Bronte V, Wang M, Overwijk WW, Surman DR, Pericle F, Rosenberg SA et al (1998) Apoptotic death of CD8+ T lymphocytes after immunization: induction of a suppressive population of Mac-1+/Gr-1+ cells. J Immunol 161(10):5313–5320

    PubMed  CAS  Google Scholar 

  17. Leenen PJ, de Bruijn MF, Voerman JS, Campbell PA, van EW (1994) Markers of mouse macrophage development detected by monoclonal antibodies. J Immunol Methods 174(1–2):5–19

    Article  PubMed  CAS  Google Scholar 

  18. Gallina G, Dolcetti L, Serafini P, De SC, Marigo I, Colombo MP et al (2006) Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. J Clin Invest 116(10):2777–2790

    Article  PubMed  CAS  Google Scholar 

  19. Huang B, Pan PY, Li Q, Sato AI, Levy DE, Bromberg J et al (2006) Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res 66(2):1123–1131

    Article  PubMed  CAS  Google Scholar 

  20. Dugast AS, Haudebourg T, Coulon F, Heslan M, Haspot F, Poirier N et al (2008) Myeloid-derived suppressor cells accumulate in kidney allograft tolerance and specifically suppress effector T cell expansion. J Immunol 180(12):7898–7906

    PubMed  CAS  Google Scholar 

  21. Rodriguez PC, Ochoa AC (2008) Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol Rev 222:180–191

    Article  PubMed  CAS  Google Scholar 

  22. Serafini P, De Santo C, Marigo I, Cingarlini S, Dolcetti L, Gallina G et al (2004) Derangement of immune responses by myeloid suppressor cells. Cancer Immunol Immunother 53(2):64–72

    Article  PubMed  CAS  Google Scholar 

  23. Donkor M, Lahue E, Hoke T, Shafer L, Coskun U, Solheim JC et al. (2009) Mammary tumor heterogeneity in the expansion of myeloid-derived suppressor cells. Int Immunopharmacol. [Epub ahead of print]

  24. Talmadge JE, Singh RK, Fidler IJ, Raz A (2007) Murine models to evaluate novel and conventional therapeutic strategies for cancer. Am J Pathol 170(3):793–804

    Article  PubMed  CAS  Google Scholar 

  25. Talmadge JE, Hood KC, Zobel LC, Shafer LR, Coles M, Toth B (2007) Chemoprevention by cyclooxygenase-2 inhibition reduces immature myeloid suppressor cell expansion. Int Immunopharmacol 7(2):140–151

    Article  PubMed  CAS  Google Scholar 

  26. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25(4):402–408

    Article  PubMed  CAS  Google Scholar 

  27. Guy CT, Cardiff RD, Muller WJ (1996) Activated neu induces rapid tumor progression. J Biol Chem 271(13):7673–7678

    Article  PubMed  CAS  Google Scholar 

  28. Key ME, Talmadge JE, Fogler WE, Bucana C, Fidler IJ (1982) Isolation of tumoricidal macrophages from lung melanoma metastases of mice treated systemically with liposomes containing a lipophilic derivative of muramyl dipeptide. J Natl Cancer Inst 69(5):1198

    PubMed  CAS  Google Scholar 

  29. Shojaei F, Wu X, Malik AK, Zhong C, Baldwin ME, Schanz S et al (2007) Tumor refractoriness to anti-VEGF treatment is mediated by CD11b + Gr1 + myeloid cells. Nat Biotechnol 25(8):911–920

    Article  PubMed  CAS  Google Scholar 

  30. Salomon DS, Brandt R, Ciardiello F, Normanno N (1995) Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 19(3):183–232

    Article  PubMed  CAS  Google Scholar 

  31. Bouchard L, Lamarre L, Tremblay PJ, Jolicoeur P (1989) Stochastic appearance of mammary tumors in transgenic mice carrying the MMTV/c-neu oncogene. Cell 57(6):931–936

    Article  PubMed  CAS  Google Scholar 

  32. Guy CT, Webster MA, Schaller M, Parsons TJ, Cardiff RD, Muller WJ (1992) Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci USA 89(22):10578–10582

    Article  PubMed  CAS  Google Scholar 

  33. Wellings SR, Jensen HM (1973) On the origin and progression of ductal carcinoma in the human breast. J Natl Cancer Inst 50(5):1111–1118

    PubMed  CAS  Google Scholar 

  34. Muller WJ, Sinn E, Pattengale PK, Wallace R, Leder P (1988) Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 54(1):105–115

    Article  PubMed  CAS  Google Scholar 

  35. Di CE, Diodoro MG, Boggio K, Modesti A, Modesti M, Nanni P et al (1999) Analysis of mammary carcinoma onset and progression in HER-2/neu oncogene transgenic mice reveals a lobular origin. Lab Invest 79(10):1261–1269

    Google Scholar 

  36. Boggio K, Nicoletti G, Di Carlo E, Cavallo F, Landuzzi L, Melani C et al (1998) Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of Her-2/neu transgenic mice. J Exp Med 188(3):589–596

    Article  PubMed  CAS  Google Scholar 

  37. Nanni P, Nicoletti G, De GC, Landuzzi L, Di CE, Iezzi M et al (2003) Prevention of HER-2/neu transgenic mammary carcinoma by tamoxifen plus interleukin 12. Int J Cancer 105(3):384–389

    Article  PubMed  CAS  Google Scholar 

  38. Sas S, Chan T, Sami A, El-Gayed A, Xiang J (2008) Vaccination of fiber-modified adenovirus-transfected dendritic cells to express HER-2/neu stimulates efficient HER-2/neu-specific humoral and CTL responses and reduces breast carcinogenesis in transgenic mice. Cancer Gene Ther 15(10):655–666

    Article  PubMed  CAS  Google Scholar 

  39. Singh R, Paterson Y (2006) Vaccination strategy determines the emergence and dominance of CD8+ T-cell epitopes in a FVB/N rat HER-2/neu mouse model of breast cancer. Cancer Res 66(15):7748–7757

    Article  PubMed  CAS  Google Scholar 

  40. Boggio K, Di CE, Rovero S, Cavallo F, Quaglino E, Lollini PL et al (2000) Ability of systemic interleukin-12 to hamper progressive stages of mammary carcinogenesis in HER2/neu transgenic mice. Cancer Res 60(2):359–364

    PubMed  CAS  Google Scholar 

  41. Cipriani B, Fridman A, Bendtsen C, Dharmapuri S, Mennuni C, Pak I et al (2008) Therapeutic vaccination halts disease progression in BALB-neuT mice: the amplitude of elicited immune response is predictive of vaccine efficacy. Hum Gene Ther 19(7):670–680

    Article  PubMed  CAS  Google Scholar 

  42. Street SE, Zerafa N, Iezzi M, Westwood JA, Stagg J, Musiani P et al (2007) Host perforin reduces tumor number but does not increase survival in oncogene-driven mammary adenocarcinoma. Cancer Res 67(11):5454–5460

    Article  PubMed  CAS  Google Scholar 

  43. Henry MD, Triplett AA, Oh KB, Smith GH, Wagner KU (2004) Parity-induced mammary epithelial cells facilitate tumorigenesis in MMTV-neu transgenic mice. Oncogene 23(41):6980–6985

    Article  PubMed  CAS  Google Scholar 

  44. Landis MD, Seachrist DD, Abdul-Karim FW, Keri RA (2006) Sustained trophism of the mammary gland is sufficient to accelerate and synchronize development of ErbB2/Neu-induced tumors. Oncogene 25(23):3325–3334

    Article  PubMed  CAS  Google Scholar 

  45. Estrov Z, Talpaz M, Mavligit G, Pazdur R, Harris D, Greenberg SM et al (1995) Elevated plasma thrombopoietic activity in patients with metastatic cancer-related thrombocytosis. Am J Med 98(6):551–558

    Article  PubMed  CAS  Google Scholar 

  46. Kitamura H, Kodama F, Odagiri S, Nagahara N, Inoue T, Kanisawa M (1989) Granulocytosis associated with malignant neoplasms: a clinicopathologic study and demonstration of colony-stimulating activity in tumor extracts. Hum Pathol 20(9):878–885

    Article  PubMed  CAS  Google Scholar 

  47. Ruka W, Rutkowski P, Kaminska J, Rysinska A, Steffen J (2001) Alterations of routine blood tests in adult patients with soft tissue sarcomas: relationships to cytokine serum levels and prognostic significance. Ann Oncol 12(10):1423–1432

    Article  PubMed  CAS  Google Scholar 

  48. Fu YX, Watson G, Jimenez JJ, Wang Y, Lopez DM (1990) Expansion of immunoregulatory macrophages by granulocyte-macrophage colony-stimulating factor derived from a murine mammary tumor. Cancer Res 50(2):227–234

    PubMed  CAS  Google Scholar 

  49. Pan PY, Wang GX, Yin B, Ozao J, Ku T, Divino CM et al (2008) Reversion of immune tolerance in advanced malignancy: modulation of myeloid-derived suppressor cell development by blockade of stem-cell factor function. Blood 111(1):219–228

    Article  PubMed  CAS  Google Scholar 

  50. Bronte V, Chappell DB, Apolloni E, Cabrelle A, Wang M, Hwu P et al (1999) Unopposed production of granulocyte-macrophage colony-stimulating factor by tumors inhibits CD8+ T cell responses by dysregulating antigen-presenting cell maturation. J Immunol 162(10):5728–5737

    PubMed  CAS  Google Scholar 

  51. Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S et al (1996) Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 2(10):1096–1103

    Article  PubMed  CAS  Google Scholar 

  52. Oyama T, Ran S, Ishida T, Nadaf S, Kerr L, Carbone DP et al (1998) Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. J Immunol 160(3):1224–1232

    PubMed  CAS  Google Scholar 

  53. Young MR, Kolesiak K, Wright MA, Gabrilovich DI (1999) Chemoattraction of femoral CD34+ progenitor cells by tumor-derived vascular endothelial cell growth factor. Clin Exp Metastasis 17(10):881–888

    Article  PubMed  CAS  Google Scholar 

  54. Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ (2009) Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy. Cancer Immunol Immunother 58(1):49–59

    Article  PubMed  CAS  Google Scholar 

  55. Ochoa AC, Zea AH, Hernandez C, Rodriguez PC (2007) Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res 13(2 Pt 2):721s–726s

    Article  PubMed  CAS  Google Scholar 

  56. Marty M, Pivot X (2008) The potential of anti-vascular endothelial growth factor therapy in metastatic breast cancer: clinical experience with anti-angiogenic agents, focusing on bevacizumab. Eur J Cancer 44(7):912–920

    Article  PubMed  CAS  Google Scholar 

  57. Krishnamurthy S, Sneige N (2002) Molecular and biologic markers of premalignant lesions of human breast. Adv Anat Pathol 9(3):185–197

    Article  PubMed  Google Scholar 

  58. Melani C, Sangaletti S, Barazzetta FM, Werb Z, Colombo MP (2007) Amino-biphosphonate-mediated MMP-9 inhibition breaks the tumor-bone marrow axis responsible for myeloid-derived suppressor cell expansion and macrophage infiltration in tumor stroma. Cancer Res 67(23):11438–11446

    Article  PubMed  CAS  Google Scholar 

  59. Gabrilovich DI, Bronte V, Chen SH, Colombo MP, Ochoa A, Ostrand-Rosenberg S et al (2007) The terminology issue for myeloid-derived suppressor cells. Cancer Res 67(1):425

    Article  PubMed  CAS  Google Scholar 

  60. Kusmartsev S, Gabrilovich DI (2002) Immature myeloid cells and cancer-associated immune suppression. Cancer Immunol Immunother 51(6):293–298

    Article  PubMed  CAS  Google Scholar 

  61. Solheim JC, Reber AJ, Ashour AE, Robinson S, Futakuchi M, Kurz SG et al (2007) Spleen but not tumor infiltration by dendritic and T cells is increased by intravenous adenovirus-Flt3 ligand injection. Cancer Gene Ther 14(4):364–371

    Article  PubMed  CAS  Google Scholar 

  62. Gabrilovich DI, Velders MP, Sotomayor EM, Kast WM (2001) Mechanism of immune dysfunction in cancer mediated by immature Gr-1+ myeloid cells. J Immunol 166(9):5398–5406

    PubMed  CAS  Google Scholar 

  63. Kusmartsev S, Eruslanov E, Kubler H, Tseng T, Sakai Y, Su Z et al (2008) Oxidative stress regulates expression of VEGFR1 in myeloid cells: link to tumor-induced immune suppression in renal cell carcinoma. J Immunol 181(1):346–353

    PubMed  CAS  Google Scholar 

  64. Reilly RT, Gottlieb MB, Ercolini AM, Machiels JP, Kane CE, Okoye FI et al (2000) HER-2/neu is a tumor rejection target in tolerized HER-2/neu transgenic mice. Cancer Res 60(13):3569–3576

    PubMed  CAS  Google Scholar 

  65. Serafini P, Carbley R, Noonan KA, Tan G, Bronte V, Borrello I (2004) High-dose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells. Cancer Res 64(17):6337–6343

    Article  PubMed  CAS  Google Scholar 

  66. Parmiani G, Castelli C, Pilla L, Santinami M, Colombo MP, Rivoltini L (2007) Opposite immune functions of GM-CSF administered as vaccine adjuvant in cancer patients. Ann Oncol 18(2):226–232

    Article  PubMed  CAS  Google Scholar 

  67. Reber AJ, Ashour AE, Robinson SN, Talmadge JE, Solheim JC (2004) Flt3 ligand bioactivity and pharmacology in neoplasia. Curr Drug Targets Immune Endocr Metabol Disord 4(2):149–156

    Article  PubMed  CAS  Google Scholar 

  68. Calogero RA, Cordero F, Forni G, Cavallo F (2007) Inflammation and breast cancer. Inflammatory component of mammary carcinogenesis in ErbB2 transgenic mice. Breast Cancer Res 9(4):211

    Article  PubMed  CAS  Google Scholar 

  69. Worschech A, Kmieciak M, Knutson KL, Bear HD, Szalay AA, Wang E et al (2008) Signatures associated with rejection or recurrence in HER-2/neu-positive mammary tumors. Cancer Res 68(7):2436–2446

    Article  PubMed  CAS  Google Scholar 

  70. Astolfi A, Landuzzi L, Nicoletti G, De GC, Croci S, Palladini A et al (2005) Gene expression analysis of immune-mediated arrest of tumorigenesis in a transgenic mouse model of HER-2/neu-positive basal-like mammary carcinoma. Am J Pathol 166(4):1205–1216

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

3419012108027 Avon—Adenovirus p53 Infected DC Vaccine for Breast Cancer. 3132050740—Nebraska Research Initiative—“Translation of Biotechnology into the Clinic”. The authors would like to thank Miss Jill Hallgren for editing of the manuscript.

Author information

Authors and Affiliations

  1. Laboratory of Transplantation Immunology, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-7660, USA

    Fuminori Abe, Alicia J. Dafferner, Moses Donkor, Sherry N. Westphal, Eric M. Scholar, Joyce C. Solheim, Rakesh K. Singh, Traci A. Hoke & James E. Talmadge

Authors
  1. Fuminori Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alicia J. Dafferner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Moses Donkor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sherry N. Westphal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eric M. Scholar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joyce C. Solheim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rakesh K. Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Traci A. Hoke
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. James E. Talmadge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James E. Talmadge.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material (PDF 64 KB)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abe, F., Dafferner, A.J., Donkor, M. et al. Myeloid-derived suppressor cells in mammary tumor progression in FVB Neu transgenic mice. Cancer Immunol Immunother 59, 47–62 (2010). https://doi.org/10.1007/s00262-009-0719-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-009-0719-2

Keywords

Search

Navigation