Institut für Pathologie Nordhessen, Germaniastrasse 7-9, Kassel, Germany.
BMC Cancer. 2010 Oct 22;10:578. doi: 10.1186/1471-2407-10-578.
Renal cell carcinoma (RCC) represents one of the most immunoresponsive cancers. Antigen-specific vaccination with dendritic cells (DCs) in patients with metastatic RCC has been shown to induce cytotoxic T-cell responses associated with objective clinical responses. Thus, clinical trials utilizing DCs for immunotherapy of advanced RCCs appear to be promising; however, detailed analyses concerning the distribution and function of DC subsets in RCCs are lacking.
We characterized the distribution of the different immature and mature myeloid DC subsets in RCC tumour tissue and the corresponding normal kidney tissues. In further analyses, the expression of various chemokines and chemokine receptors controlling the migration of DC subsets was investigated.
The highest numbers of immature CD1a+ DCs were found within RCC tumour tissue. In contrast, the accumulation of mature CD83+/DC-LAMP+ DCs were restricted to the invasive margin of the RCCs. The mature DCs formed clusters with proliferating T-cells. Furthermore, a close association was observed between MIP-3α-producing tumour cells and immature CCR6+ DC recruitment to the tumour bed. Conversely, MIP-3β and SLC expression was only detected at the tumour border, where CCR7-expressing T-cells and mature DCs formed clusters.
Increased numbers of immature DCs were observed within the tumour tissue of RCCs, whereas mature DCs were found in increased numbers at the tumour margin. Our results strongly implicate that the distribution of DC subsets is controlled by local lymphoid chemokine expression. Thus, increased expression of MIP-3α favours recruitment of immature DCs to the tumour bed, whereas de novo local expression of SLC and MIP-3β induces accumulation of mature DCs at the tumour margin forming clusters with proliferating T-cells reflecting a local anti-tumour immune response.
肾细胞癌 (RCC) 是最具免疫反应性的癌症之一。在转移性 RCC 患者中，用树突状细胞 (DC) 进行抗原特异性疫苗接种已被证明可诱导与客观临床反应相关的细胞毒性 T 细胞反应。因此，利用 DC 进行晚期 RCC 免疫治疗的临床试验似乎很有前途；然而，缺乏关于 RCC 中 DC 亚群分布和功能的详细分析。
我们描述了不同未成熟和成熟髓样 DC 亚群在 RCC 肿瘤组织和相应正常肾组织中的分布。在进一步的分析中，研究了控制 DC 亚群迁移的各种趋化因子和趋化因子受体的表达。
在 RCC 肿瘤组织中发现了数量最多的不成熟 CD1a+ DC。相比之下，成熟 CD83+/DC-LAMP+ DC 的聚集仅限于 RCC 的浸润边缘。成熟的 DC 与增殖的 T 细胞形成簇。此外，还观察到产生 MIP-3α 的肿瘤细胞与不成熟的 CCR6+ DC 募集到肿瘤床之间存在密切关联。相反，MIP-3β 和 SLC 的表达仅在肿瘤边界检测到，在那里 CCR7 表达的 T 细胞和成熟的 DC 形成簇。
在 RCC 的肿瘤组织中观察到未成熟 DC 的数量增加，而在肿瘤边缘发现成熟 DC 的数量增加。我们的结果强烈表明，DC 亚群的分布受局部淋巴趋化因子表达的控制。因此，MIP-3α 的表达增加有利于未成熟 DC 募集到肿瘤床，而 SLC 和 MIP-3β 的局部新表达则导致成熟 DC 在肿瘤边缘积聚，与增殖的 T 细胞形成簇，反映了局部抗肿瘤免疫反应。
