O'Donnell Rebekah K, Mick Rosemarie, Feldman Michael, Hino Satoshi, Wang Yan, Brose Marcia S, Muschel Ruth J
Department of Pathology, Children's Hospital of Philadelphia, PA, USA.
Cancer Lett. 2007 Sep 18;255(1):145-52. doi: 10.1016/j.canlet.2007.04.003. Epub 2007 Jun 18.
Dendritic cell (DC) function will likely be important for immunological cancer therapies, but our knowledge of the roles of DCs in tumors is limited, in part because most studies were performed before DC subtypes were defined. We studied the distributions of immature epidermal, immature dermal, mature, and plasmacytoid DCs in 63 primary tumors and eight lymph node metastases from oral squamous cell carcinoma patients without evidence of distant metastasis. Immature CD207/Langerin+ and CD209/DC-SIGN+ DCs were present in the primary tumor region, but CD209/DC-SIGN+ cells rarely infiltrated the tumor. Mature DCs were rare, and presence of CD123+ plasmacytoid DCs was associated with poorer outcome. Unexpectedly, migration and maturation of DCs was associated with a worse outcome. Overall, the distribution of DC subtypes indicated that ineffective DC response to tumor is a failure of DC function rather than recruitment, suggesting that a strategy of shifting the balance of secreted factors in the tumor milieu may be more effective in restoring anti-tumor immune function than current methods restoring only one population of DCs to the immunosuppressive tumor region.
树突状细胞(DC)功能可能对免疫性癌症治疗很重要,但我们对DC在肿瘤中作用的了解有限,部分原因是大多数研究是在DC亚型被定义之前进行的。我们研究了63例原发性肿瘤和8例来自无远处转移证据的口腔鳞状细胞癌患者的淋巴结转移灶中未成熟表皮DC、未成熟真皮DC、成熟DC和浆细胞样DC的分布情况。未成熟的CD207/朗格汉斯蛋白阳性和CD209/DC-SIGN阳性DC存在于原发性肿瘤区域,但CD209/DC-SIGN阳性细胞很少浸润肿瘤。成熟DC很少见,且CD123阳性浆细胞样DC的存在与较差的预后相关。出乎意料的是,DC的迁移和成熟与较差的预后相关。总体而言,DC亚型的分布表明,DC对肿瘤的无效反应是DC功能的失败而非募集失败,这表明改变肿瘤微环境中分泌因子平衡的策略可能比目前仅将一种DC群体恢复到免疫抑制性肿瘤区域的方法在恢复抗肿瘤免疫功能方面更有效。