Thurnher M, Radmayr C, Ramoner R, Ebner S, Böck G, Klocker H, Romani N, Bartsch G
Department of Urology, University of Innsbruck, Austria.
Int J Cancer. 1996 Sep 27;68(1):1-7. doi: 10.1002/(SICI)1097-0215(19960927)68:1<1::AID-IJC1>3.0.CO;2-V.
Immune surveillance of cancer requires antigen-presenting cells which activate T cells specific for tumor-associated antigens. We show here that substantial numbers of dendritic cells, which are the most potent antigen-presenting cells, emigrate from renal-tumor explants in organ culture. Tumor-derived dendritic cells presented with all characteristics of mature dendritic cells. Dendritic cells could be identified by typical cytoplasmic projections (=veils). They expressed high levels of MHC products and of the co-stimulator CD86 (B7-2). Dendritic cells expressed the CD45RO isoform but not CD45RA. The most important point was that up to 9% of the emigrating leukocytes expressed the CD83 antigen, a specific marker for mature dendritic cells. CD83+ cells were approximately 40-fold enriched in the tumor tissue as compared to the peripheral blood. In contrast to cultured blood dendritic cells, tumor-emigrant dendritic cells had a reduced potential to capture soluble antigen, as shown by the exclusion of fluoresceinated Dextran molecules. Finally, in mixed leukocyte reactions, tumor-derived dendritic cells were able to stimulate naive T cells from cord blood, which is a unique feature of dendritic cells. This study demonstrates that genuine dendritic cells reside in or infiltrate renal-cell carcinoma tissue. The failure of patients with renal-cell carcinoma to mount an anti-tumor immune response despite the presence of professional antigen-presenting cells in the tumor tissue suggests that tumor-associated dendritic cells are suppressed in situ, in a similar way to that described for tumor-infiltrating lymphocytes.
癌症的免疫监视需要抗原呈递细胞来激活针对肿瘤相关抗原的特异性T细胞。我们在此表明,大量最有效的抗原呈递细胞——树突状细胞,在器官培养中从肾肿瘤外植体中迁出。肿瘤来源的树突状细胞呈现出成熟树突状细胞的所有特征。树突状细胞可通过典型的细胞质突起(=面纱)来识别。它们高水平表达MHC产物和共刺激分子CD86(B7-2)。树突状细胞表达CD45RO异构体,但不表达CD45RA。最重要的一点是,高达9%的迁出白细胞表达CD83抗原,这是成熟树突状细胞的特异性标志物。与外周血相比,肿瘤组织中CD83+细胞富集了约40倍。与培养的血液树突状细胞相比,肿瘤迁出的树突状细胞捕获可溶性抗原的能力降低,这通过排除荧光素标记的葡聚糖分子得以证明。最后,在混合白细胞反应中,肿瘤来源的树突状细胞能够刺激脐血中的幼稚T细胞,这是树突状细胞的一个独特特征。这项研究表明,真正的树突状细胞存在于肾细胞癌组织中或浸润其中。尽管肿瘤组织中存在专职抗原呈递细胞,但肾细胞癌患者未能产生抗肿瘤免疫反应,这表明肿瘤相关树突状细胞在原位受到抑制,类似于肿瘤浸润淋巴细胞的情况。