Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Cancer Immunol Immunother. 2010 Nov;59(11):1645-53. doi: 10.1007/s00262-010-0890-5. Epub 2010 Jul 6.
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-1beta and TNF-alpha 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-1beta and partially inhibited by the neutralization of IL-1beta. 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-1beta in response to tumor supernatants.
肿瘤的微环境会抑制免疫系统，诱导树突状细胞（DC）发生改变，但对于血液恶性肿瘤，相关信息却很匮乏。本研究旨在研究白血病细胞产物对 DC 分化的影响。采集健康志愿者的单核细胞，在 IL-4 和 GM-CSF 的存在下培养以生成未成熟的 DC。在分化过程中，将白血病培养物的上清液加入单核细胞培养物中。所使用的细胞系包括慢性髓性白血病的 K562、早幼粒细胞白血病的 HL-60 和源自 Burkitt 淋巴瘤的 DAUDI。结果观察到，存在肿瘤上清液时，CD14 的表达仍然较高，而 CD1a 则较低，而非恶性上清液则不会影响这些参数。此外，肿瘤上清液的存在增加了单核细胞在分化过程中产生 IL-1beta 和 TNF-alpha。CD14 和 CD1a 表达的改变可以通过添加外源性 IL-1beta 来模拟，并且可以部分通过中和 IL-1beta 来抑制。这些结果表明，白血病细胞的可溶性产物会干扰 DC 的分化，在本研究中，这种效应可能是由肿瘤上清液刺激单核细胞产生的 IL-1beta 介导的。
