Skip to main content

Differences in Dendritic Cell Activation and Distribution After Intravenous, Intraperitoneal, and Subcutaneous Injection of Lymphoma Cells in Mice

  • Conference paper
Immune-Mediated Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 601))

  • 2315 Accesses

Abstract

Dendritic cells (DCs) are key antigen-presenting cells (APCs) for initiating immune responses. However, in recent years, several groups have shown the defective function of DCs in tumor-bearing mice and in cancer patients. Our aim was to study the effects of lymphoma on DC differentiation and maturation and to assess the input of the tumor microenvironment and intravasation of tumor cells on DC precursors. EL-4 lymphoma cells were administrated via different routes (intraperitoneal, subcutaneous, and intravenous) and DC phenotype was investigated. Bone marrow-derived DCs and APCs obtained from the spleen were examined by flow cytometry, and immunohistochemical analysis of lymphoma, lungs, livers, and spleens was also performed. Intravenous administration of lymphoma cells induced suppression of DC differentiation and maturation assessed as a significant decrease of the IAb, CD80, CD86, CD11b, and CD11c expression on DCs and IAb on splenic APCs. Up-regulation of APC differentiation was observed in animals after subcutaneous and intraperitoneal administration of lymphoma cells determined as increased expression of CD40 and CD86 in spleen APCs. These data suggest that the development of antitumor immune response might differ in the host receiving tumor vaccines via different injection routes.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Almand, B., Resser, J.R., Lindman, B., Nadaf, S., Clark, J.I., Kwon, E.D., Carbone D.P. and Gabrilovich, D.I. (2000) Clinical significance of defective dendritic cell differentiation in cancer. Clin. Cancer Res. 6, 1755–1766.

    CAS  PubMed  Google Scholar 

  • Caux, C., Vanbervliet, B., Massacrier, C., Azuma, M., Okumura, K., Lanier, L.L. and Banchereau, J. (1994) B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J. Exp. Med. 180, 1841–1847.

    Article  CAS  PubMed  Google Scholar 

  • Chaux, P., Favre, N. and Martin, M. (1997) Tumor-infiltrating dendritic cells are defective in their antigen-presenting function and inducible B7 expression in rats. Int. J. Cancer 72, 619–624.

    Article  CAS  PubMed  Google Scholar 

  • Chaux, P., Moutet, M., Faivre, J. and Martin, F. (1996) Inflammatory cells infiltrating human colorectal carcinomas express HLA class II but not B7-1 and B7-2 costimulatory molecules of the T cell activation. Lab. Invest. 74, 975–983.

    CAS  PubMed  Google Scholar 

  • Della Bella, S., Gennaro, M., Vaccari, M., Ferraris, C., Nicola, S., Riva, A., Clerici, M., Greco, M. and Villa, M.L. (2003) Altered maturation of peripheral blood dendritic cells in patients with breast cancer. Br. J. Cancer 89, 1463–1472.

    Article  CAS  PubMed  Google Scholar 

  • Esche, C., Lokshin, A., Shurin, G.V., Gastman, B.R., Rabinowich, H., Watkins, S.C., Lotze, M.T. and Shurin, M.R. (1999) Tumor’s other immune targets, dendritic cells. J. Leukoc. Biol. 66, 336–344.

    CAS  PubMed  Google Scholar 

  • Ferreri, A.J., Campo, E., Seymour, J.F., Willemze, R., Ilariucci, F., Ambrosetti, A., Zucca, E., Rossi, G., Lopez-Guillermo, A., Pavlovsky, M.A., Geerts, M.L., Candoni, A., Lestani, M., Asioli, S., Milani, M., Piris, M.A., Pileri, S., Facchetti, F., Cavalli, F., Ponzoni, M. and International Extranodal Lymphoma Study Group (IELSG). (2004) Intravascular lymphoma, clinical presentation, natural history, management and prognostic factors in a series of 38 cases, with special emphasis on the ‘cutaneous variant’. Br. J. Haematol. 127, 173–183.

    Article  PubMed  Google Scholar 

  • Gabrilovich, D.I., Chen, H.L., Girgis, K.R. and Cunningham, H.T. (1996a) Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat. Med. 2, 1096–1103.

    Article  CAS  PubMed  Google Scholar 

  • Gabrilovich, D.I., Ciernik, I.F. and Carbone, D.P. (1996b) Dendritic cells in antitumor immune responses 1 defective antigen presentation in tumor-bearing hosts. Cell. Immunol. 170, 101–110.

    Google Scholar 

  • Gabrilovich, D.I., Corak, J., Ciernik, I.F., Kavanaugh, D. and Carbone, D.P. (1997) Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin. Cancer Res. 3, 483–490.

    CAS  PubMed  Google Scholar 

  • Gerlini, G., Tun-Kyi, A., Dudli, C., Burg, G., Pimpinelli, N. and Nestle, F.O. (2004) Metastatic melanoma secreted IL-10 down-regulates CD1 molecules on dendritic cells in metastatic tumor lesions. Am. J. Pathol. 165, 1853–1863.

    CAS  PubMed  Google Scholar 

  • Goodlad, J.R., Krajewski, A.S., Batstone, P.J., McKay, P., White, J.M., Benton, E.C., Kavanagh, G.M., Lucraft, H.H. and Scotland and Newcastle Lymphoma Group (2003) Primary cutaneous diffuse large B cell lymphoma, prognostic significance of clinicopathological subtypes. Am. J. Surg. Pathol. 27, 1538–1545.

    Article  PubMed  Google Scholar 

  • Hart, D.N.J. (1997) Dendritic cells, unique leucocyte populations which control the primary immune response. Blood 90, 3245–3287.

    CAS  PubMed  Google Scholar 

  • Hegde, S., Pahne, J. and Smola-Hess, S. (2004) Novel immunosuppressive properties of interleukin-6 in dendritic cells, inhibition of NF-kappaB binding activity and CCR7 expression. FASEB J. 18, 1439–1441.

    CAS  PubMed  Google Scholar 

  • Ishida, T., Oyama, T., Carbone, D. and Gabrilovich, D.I. (1998) Defective function of Langerhans cells in tumor-bearing animals is the result of defective maturation from hematopoietic progenitors. J. Immunol. 161, 4842–4851.

    CAS  PubMed  Google Scholar 

  • Ko, Y.H., Cho, E.Y., Kim, J.E., Lee, S.S., Huh, J.R., Chang, H.K., Yang, W.I., Kim, C.W., Kim, S.W. and Ree, H.J. (2004) NK and NK-like T cell lymphoma in extranasal sites, a comparative clinicopathological study according to site and EBV status. Histopathology 44, 480–489.

    Article  CAS  PubMed  Google Scholar 

  • McKechnie, A., Robins, R.A. and Eremin, O. (2004) Immunological aspects of head and neck cancer, biology, pathophysiology and therapeutic mechanisms. Surgeon 2, 187–207.

    Article  CAS  PubMed  Google Scholar 

  • Nestle, F.O., Burg, G., Fah, J., Wrone-Smith, T. and Nickoloff, B.J. (1997) Human sunlight-induced basal-cell-carcinoma-associated dendritic cells are deficient in T cell co-stimulatory molecules and are impaired as antigen-presenting cells. Am. J. Pathol. 150, 641–651.

    CAS  PubMed  Google Scholar 

  • Neves, A.R., Ensina, L.F., Anselmo, L.B., Leite, K.R., Buzaid, A.C., Camara-Lopes, L.H. and Barbuto, J.A. (2005) Dendritic cells derived from metastatic cancer patients vaccinated with allogeneic dendritic cell-autologous tumor cell hybrids express more CD86 and induce higher levels of interferon-gamma in mixed lymphocyte reactions. Cancer Immunol. Immunother. 54, 61–66.

    Article  CAS  PubMed  Google Scholar 

  • Ohm, J.E. and Carbone, D.P. (2001) VEGF as a mediator of tumor-associated immunodeficiency. Immunol. Res. 23, 263–272.

    Article  CAS  PubMed  Google Scholar 

  • Platsoucas, C.D., Fincke, J.E., Pappas, J., Jung, W.J., Heckel, M., Schwarting, R., Magira, E., Monos, D. and Freedman, R.S. (2003) Immune responses to human tumors, development of tumor vaccines. Anticancer Res. 23, 1969–1996.

    CAS  PubMed  Google Scholar 

  • Pospisilova, D., Borovickova, J., Rozkova, D., Stary, J., Seifertova, D., Tobiasova, Z., Spisek, R. and Bartunkova, J. (2005) Methods of dendritic cell preparation for acute lymphoblastic leukaemia immunotherapy in children. Med. Oncol. 22, 79–88.

    Article  CAS  PubMed  Google Scholar 

  • Qin, Z., Noffz, G., Mohaupt, M. and Blankenstein, T. (1997) Interleukin-10 prevents dendritic cell accumulation and vaccination with granulocyte-macrophage colonystimulating factor gene-modified tumor cells. J. Immunol. 159, 770–776.

    CAS  PubMed  Google Scholar 

  • Sharma, S., Stolina, M., Yang, S.C., Baratelli, F., Lin, J.F., Atianzar, K., Luo, J., Zhu, L., Lin, Y., Huang, M., Dohadwala, M., Batra, R.K. and Dubinett, S.M. (2003) Tumor cyclooxygenase 2-dependent suppression of dendritic cell function. Clin. Cancer Res. 9, 961–968.

    CAS  PubMed  Google Scholar 

  • Shurin, M.R., Yurkovetsky, Z.R., Tourkova, I.L., Balkir, L. and Shurin, G.V. (2002) Inhibition of CD40 expression and CD40-mediated dendritic cell function by tumor-derived IL-10. Int. J. Cancer 101, 61–68.

    Article  CAS  PubMed  Google Scholar 

  • ten Berge, R.L., Oudejans, J.J., Ossenkoppele, G.J., Pulford, K., Willemze, R., Falini, B., Chott, A. and Meijer, C.J. (2000) ALK expression in extranodal anaplastic large cell lymphoma favours systemic disease with (primary) nodal involvement and a good prognosis and occurs before dissemination. J. Clin. Pathol. 53, 445–450.

    Article  PubMed  Google Scholar 

  • Tsuge, K., Takeda, H., Kawada, S., Maeda, K. and Yamakawa, M. (2005) Characterization of dendritic cells in differentiated thyroid cancer. J. Pathol. 205, 565–576.

    Article  CAS  PubMed  Google Scholar 

  • Weber, F., Byrne, S.N., Le, S., Brown, D.A., Breit, S.N., Scolyer, R.A. and Halliday, G.M. (2005) Transforming growth factor-beta1 immobilises dendritic cells within skin tumours and facilitates tumour escape from the immune system. Cancer Immunol. Immunother. 54, 898–906.

    Article  CAS  PubMed  Google Scholar 

  • Yang, A.S. and Lattime, E.C. (2003) Tumor-induced interleukin 10 suppresses the ability of splenic dendritic cells to stimulate CD4 and CD8 T cell responses. Cancer Res. 63, 2150–2157.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Valentin Gerein .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer Science+Business Media, LLC

About this paper

Cite this paper

Sevko, A.L., Barysik, N., Perez, L., Shurin, M.R., Gerein, V. (2007). Differences in Dendritic Cell Activation and Distribution After Intravenous, Intraperitoneal, and Subcutaneous Injection of Lymphoma Cells in Mice. In: Shurin, M.R., Smolkin, Y.S. (eds) Immune-Mediated Diseases. Advances in Experimental Medicine and Biology, vol 601. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72005-0_27

Download citation

Publish with us

Policies and ethics