Skip to main content

Advertisement

SpringerLink
Log in

Leukemic cell products down-regulate human dendritic cell differentiation

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

Abstract

The microenvironment produced by solid tumors is inhibitory to the immune system, inducing dendritic cell (DC) alterations, but there is a paucity of information regarding haematological malignances. The aim of this study was to investigate DC differentiation under the influence of leukemic cell products. Monocytes from healthy volunteers were cultured in the presence of IL-4 and GM-CSF for the generation of immature DCs. Supernatants from leukemic cultures were added to monocyte cultures during differentiation. The lineages used were K562, a chronic myeloid leukemia, HL-60, a promyelocytic leukemia and DAUDI, originated from Burkitt lymphoma. It was observed that the expression of CD14 remained high and the CD1a was low in the presence of tumor supernatants, while non-malignant supernatants did not affect these parameters. Furthermore, IL-1β and TNF-α production by monocytes during differentiation was increased by the presence of tumor supernatants. The modifications on CD14 and CD1a expressions could be mimicked by the addition of exogenous IL-1β and partially inhibited by the neutralization of IL-1β. These results suggest that soluble products from leukemic cells interfere with DC differentiation and, in the present work, this effect could be mediated by monocyte-derived IL-1β in response to tumor supernatants.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Biemer JJ (1990) Malignant lymphomas associated with immunodeficiency states. Ann Clin Lab Sci 20:175–191

    CAS  PubMed  Google Scholar 

  2. Dranoff G (2004) Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer 4:11–22

    Article  CAS  PubMed  Google Scholar 

  3. Shunyakov L, Ryan CK, Sahasrabudhe DM, Khorana AA (2004) The influence of host response on colorectal cancer prognosis. Clin Colorectal Cancer 4:38–45

    Article  CAS  PubMed  Google Scholar 

  4. Costello RT, Gastaut JA, Olive D (1999) Mechanisms of tumor escape from immunologic response. Rev Med Interne 20:579–588

    Article  CAS  PubMed  Google Scholar 

  5. Algarra I, García-Lora A, Cabrera T, Ruiz-Cabello F, Garrido F (2004) The selection of tumor variants with altered expression of classical and nonclassical MHC class I molecules: implications for tumor immune escape. Cancer Immunol Immunother 53:904–910

    Article  CAS  PubMed  Google Scholar 

  6. Shurin M, Gabrilovich D (2001) Regulation of the dendritic cell system by tumor. Cancer Res Ther Control 11:65–78

    Google Scholar 

  7. Zou W (2005) Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 5:263–274

    Article  CAS  PubMed  Google Scholar 

  8. Elgert KD, Alleva DG, Mullins DW (1998) Tumor-induced immune dysfunction: the macrophage connection. J Leukoc Biol 64:275–290

    CAS  PubMed  Google Scholar 

  9. Chomarat P, Banchereau J, Davoust J, Palucka AK (2000) IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nat Immunol 1:510–514

    Article  CAS  PubMed  Google Scholar 

  10. Allavena P, Piemonti L, Longoni D, Bernasconi S, Stoppacciaro A, Ruco L, Mantovani A (1998) IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages. Eur J Immunol 28:359–369

    Article  CAS  PubMed  Google Scholar 

  11. Kalinski P, Schuitemaker JH, Hilkens CM, Kapsenberg ML (1998) Prostaglandin E2 induces the final maturation of IL-12-deficient CD1a+CD83+ dendritic cells: the levels of IL-12 are determined during the final dendritic cell maturation and are resistant to further modulation. J Immunol 161:2804–2809

    CAS  PubMed  Google Scholar 

  12. Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252

    Article  CAS  PubMed  Google Scholar 

  13. Romani N, Gruner S, Brang D, Kämpgen E, Lenz A, Trockenbacher B, Konwalinka G, Fritsch PO, Steinman RM, Schuler G (1994) Proliferating dendritic cell progenitors in human blood. J Exp Med 180:83–93

    Article  CAS  PubMed  Google Scholar 

  14. Peters JH, Gieseler R, Thiele B, Steinbach F (1996) Dendritic cells: from ontogenetic orphans to myelomonocytic descendants. Immunol Today 17:273–278

    Article  CAS  PubMed  Google Scholar 

  15. Romani N, Reider D, Heuer M, Ebner S, Kämpgen E, Eibl B, Niederwieser D, Schuler G (1996) Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J Immunol Methods 196:137–151

    Article  CAS  PubMed  Google Scholar 

  16. Aalamian M, Tourkova IL, Chatta GS, Lilja H, Huland E, Huland H, Shurin GV, Shurin MR (2003) Inhibition of dendropoiesis by tumor derived and purified prostate specific antigen. J Urol 170:2026–2030

    Article  CAS  PubMed  Google Scholar 

  17. Shurin GV, Shurin MR, Bykovskaia S, Shogan J, Lotze MT, Barksdale EM Jr (2001) Neuroblastoma-derived gangliosides inhibit dendritic cell generation and function. Cancer Res 61:363–369

    CAS  PubMed  Google Scholar 

  18. Menetrier-Caux C, Montmain G, Dieu MC, Bain C, Favrot MC, Caux C, Blay JY (1998) Inhibition of the differentiation of dendritic cells from CD34(+) progenitors by tumor cells: role of interleukin-6 and macrophage colony-stimulating factor. Blood 92:4778–4791

    CAS  PubMed  Google Scholar 

  19. Bharadwaj U, Li M, Zhang R, Chen C, Yao Q (2007) Elevated interleukin-6 and G-CSF in human pancreatic cancer cell conditioned medium suppress dendritic cell differentiation and activation. Cancer Res 67:5479–5488

    Article  CAS  PubMed  Google Scholar 

  20. Lin WW, Karin M (2007) A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 117:1175–1183

    Article  CAS  PubMed  Google Scholar 

  21. Apte RN, Dotan S, Elkabets M, White MR, Reich E, Carmi Y, Song X, Dvozkin T, Krelin Y, Voronov E (2006) The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions. Cancer Metastasis Rev 25:387–408

    Article  CAS  PubMed  Google Scholar 

  22. Zhou LJ, Tedder TF (1996) CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. Proc Natl Acad Sci USA 93:2588–2592

    Article  CAS  PubMed  Google Scholar 

  23. Blanco P, Palucka AK, Pascual V, Banchereau J (2008) Dendritic cells and cytokines in human inflammatory and autoimmune diseases. Cytokine Growth Factor Rev 19:41–52

    Article  CAS  PubMed  Google Scholar 

  24. Sallusto F, Lanzavecchia A (1994) Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 179:1109–1118

    Article  CAS  PubMed  Google Scholar 

  25. Sombroek CC, Stam AG, Masterson AJ, Lougheed SM, Schakel MJ, Meijer CJ, Pinedo HM, van den Eertwegh AJ, Scheper RJ, de Gruijl TD (2002) Prostanoids play a major role in the primary tumor-induced inhibition of dendritic cell differentiation. J Immunol 168:4333–4343

    CAS  PubMed  Google Scholar 

  26. Kiertscher SM, Luo J, Dubinett SM, Roth MD (2000) Tumors promote altered maturation and early apoptosis of monocyte-derived dendritic cells. J Immunol 164:1269–1276

    CAS  PubMed  Google Scholar 

  27. Shurin MR, Yurkovetsky ZR, Tourkova IL, Balkir L, Shurin GV (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 

  28. Lozzio CB, Lozzio BB (1975) Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood 45:321–334

    CAS  PubMed  Google Scholar 

  29. Gallagher R, Collins S, Trujillo J, Mccredie K, Ahearn M, Tsai S, Metzgar R, Aulakh G, Ting R, Ruscetti F, Gallo R (1979) Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia. Blood 54:713–733

    CAS  PubMed  Google Scholar 

  30. Adams A, Strander H, Cantell K (1975) Sensitivity of the Epstein–Barr virus transformed human lymphoid cell lines to interferon. J Gen Virol 28:207–217

    Article  CAS  PubMed  Google Scholar 

  31. Ogden CA, Pound JD, Batth BK, Owens S, Johannessen I, Wood K, Gregory CD (2005) Enhanced apoptotic cell clearance capacity and B cell survival factor production by IL-10-activated macrophages: implications for Burkitt’s lymphoma. J Immunol 174:3015–3023

    CAS  PubMed  Google Scholar 

  32. Hillenbrand EE, Neville AM, Coventry BJ (1999) Immunohistochemical localization of CD1a-positive putative dendritic cells in human breast tumours. Br J Cancer 79:940–944

    Article  CAS  PubMed  Google Scholar 

  33. Joo HG, Fleming TP, Tanaka Y, Dunn TJ, Linehan DC, Goedegebuure PS, Eberlein TJ (2002) Human dendritic cells induce tumor-specific apoptosis by soluble factors. Int J Cancer 102:20–28

    Article  CAS  PubMed  Google Scholar 

  34. Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, Kavanaugh D, Carbone DP (1996) 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 

Download references

Acknowledgments

This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), INCT-CNPq/FAPERJ and D-MED. The authors thank Dr. Cerli Gatass and Dr. Julio Sharfstein for providing us with some reagents.

Author information

Authors and Affiliations

  1. Laboratório de Imunologia Tumoral, Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Bloco H2, Sala 003, Rio de Janeiro, 21941-590, Brazil

    Juliana Maria Motta, Clarissa Rodrigues Nascimento & Vivian Mary Rumjanek

  2. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Clarissa Rodrigues Nascimento

Authors
  1. Juliana Maria Motta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Clarissa Rodrigues Nascimento
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vivian Mary Rumjanek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vivian Mary Rumjanek.

Additional information

J. M. Motta and C. R. Nascimento contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Motta, J.M., Nascimento, C.R. & Rumjanek, V.M. Leukemic cell products down-regulate human dendritic cell differentiation. Cancer Immunol Immunother 59, 1645–1653 (2010). https://doi.org/10.1007/s00262-010-0890-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-010-0890-5

Keywords

Search

Navigation