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

  • Alexandra L. Sevko
  • Nadzeya Barysik
  • Lori Perez
  • Michael R. Shurin
  • Valentin Gerein
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 601)


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.


Dendritic Cell Costimulatory Molecule Anaplastic Large Cell Lymphoma Antitumor Immune Response Dendritic Cell Maturation 
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  1. 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.PubMedGoogle Scholar
  2. 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.CrossRefPubMedGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.PubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 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.PubMedGoogle Scholar
  7. 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.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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
  10. 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.PubMedGoogle Scholar
  11. 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.PubMedGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. Hart, D.N.J. (1997) Dendritic cells, unique leucocyte populations which control the primary immune response. Blood 90, 3245–3287.PubMedGoogle Scholar
  14. 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.PubMedGoogle Scholar
  15. 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.PubMedGoogle Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. 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.PubMedGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. Ohm, J.E. and Carbone, D.P. (2001) VEGF as a mediator of tumor-associated immunodeficiency. Immunol. Res. 23, 263–272.CrossRefPubMedGoogle Scholar
  21. 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.PubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 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.PubMedGoogle Scholar
  24. 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.PubMedGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 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.CrossRefPubMedGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Alexandra L. Sevko
    • 1
  • Nadzeya Barysik
    • 2
  • Lori Perez
    • 3
  • Michael R. Shurin
    • 3
  • Valentin Gerein
    • 4
  1. 1.R.E. Kavetsky Institute of Experimental PathologyOncology and Radiobiology, Ukrainian Academy of SciencesKyivUkraine
  2. 2.Department of Pediatric PathologyUniversity of MainzMainzGermany
  3. 3.Department of PathologyUniversity of Pittsburgh Medical CenterPittsburghUSA
  4. 4.Department of Pediatric PathologyInstitute of Pathology, University of MainzGermany

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