Top

Published in:

01-11-2010 | Original Article

Leukemic cell products down-regulate human dendritic cell differentiation

Authors: Juliana Maria Motta, Clarissa Rodrigues Nascimento, Vivian Mary Rumjanek

Published in: Cancer Immunology, Immunotherapy | Issue 11/2010

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.

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

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

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

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

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 53:904–910CrossRefPubMed

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

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

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

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

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 28:359–369CrossRefPubMed

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 161:2804–2809PubMed

12.

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

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 180:83–93CrossRefPubMed

14.

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

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 196:137–151CrossRefPubMed

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 170:2026–2030CrossRefPubMed

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 61:363–369PubMed

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 92:4778–4791PubMed

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 67:5479–5488CrossRefPubMed

20.

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

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 25:387–408CrossRefPubMed

22.

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

23.

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

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 179:1109–1118CrossRefPubMed

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 168:4333–4343PubMed

26.

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

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 101:61–68CrossRefPubMed

28.

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

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 54:713–733PubMed

30.

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

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 174:3015–3023PubMed

32.

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

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 102:20–28CrossRefPubMed

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 2:1096–1103CrossRefPubMed

Title: Leukemic cell products down-regulate human dendritic cell differentiation
Authors: Juliana Maria Motta
Clarissa Rodrigues Nascimento
Vivian Mary Rumjanek
Publication date: 01-11-2010
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 11/2010
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-010-0890-5

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 11/2010

Delivery of immunostimulatory monoclonal antibodies by encapsulated hybridoma cells

Allogeneic natural killer cells for refractory lymphoma

Integrating individual functional moieties of CXCL10 and CXCL11 into a novel chimeric chemokine leads to synergistic antitumor effects: a strategy for chemokine-based multi-target-directed cancer therapy

Differential gene expression in acute lymphoblastic leukemia cells surviving allogeneic transplant

Advances in cellular therapy: 5th International Symposium on the clinical use of cellular products, 19 and 20 March 2009, Nürnberg, Germany

A novel human recombinant single-chain antibody targeting CD166/ALCAM inhibits cancer cell invasion in vitro and in vivo tumour growth

Keynote webinar | Spotlight on antibody–drug conjugates in cancer