Hubert P, van den Brüle F, Giannini S L, Franzen-Detrooz E, Boniver J, Delvenne P
Department of Pathology, University Hospital of Liège, Liège, Belgium.
Am J Pathol. 1999 Mar;154(3):775-84. doi: 10.1016/S0002-9440(10)65324-2.
The purpose of this study was to investigate the ability of CD1a+ Langerhans/dendritic cells (LCs/DCs) to infiltrate human papillomavirus (HPV)-associated (pre)neoplastic lesions of the uterine cervix. Migration of LCs/DCs in the presence of keratinocytes derived from normal cervix and HPV-transformed cell lines was evaluated in Boyden chambers and in organotypic cultures and correlated with granulocyte/macrophage colony-stimulating factor (GM-CSF) production by the cells, as determined by ELISA. Conditioned media of HPV-transformed keratinocytes contained lower amounts of GM-CSF and induced a decreased motile response of LCs/DCs in the Boyden chamber assay compared with those of normal cervical keratinocytes. The migration of LCs/DCs in the presence of conditioned media from normal keratinocytes could be blocked by an anti-GM-CSF antibody, and the migration of LCs/DCs in the presence of conditioned media from HPV-transformed keratinocytes could be increased by supplementing the media with recombinant GM-CSF. GM-CSF was also a potent factor in enhancing the colonization of LCs/DCs into organotypic cultures of HPV-transformed keratinocytes, as the infiltration of LCs/DCs in the in vitro-formed (pre)neoplastic epithelium was minimal under basal conditions and dramatically increased after the addition of GM-CSF to the cultures. These results suggest that GM-CSF could play an important role in the recruitment of LCs/DCs into the HPV-transformed (pre)neoplastic cervical epithelium and be useful as a new immunotherapeutic approach for cervical (pre)cancers.
本研究的目的是调查CD1a +朗格汉斯细胞/树突状细胞（LCs / DCs）浸润人乳头瘤病毒（HPV）相关的子宫颈（癌前）病变的能力。在Boyden小室和器官型培养中评估了LCs / DCs在源自正常子宫颈的角质形成细胞和HPV转化细胞系存在下的迁移情况，并通过ELISA测定与细胞产生的粒细胞/巨噬细胞集落刺激因子（GM-CSF）相关联。与正常宫颈角质形成细胞相比，HPV转化的角质形成细胞的条件培养基中GM-CSF含量较低，并且在Boyden小室试验中诱导LCs / DCs的运动反应降低。抗GM-CSF抗体可阻断正常角质形成细胞条件培养基存在下LCs / DCs的迁移，而向HPV转化的角质形成细胞条件培养基中补充重组GM-CSF可增加LCs / DCs的迁移。GM-CSF也是增强LCs / DCs在HPV转化的角质形成细胞器官型培养中定植的有效因子，因为在基础条件下，LCs / DCs在体外形成的（癌前）上皮中的浸润极少，而在向培养物中添加GM-CSF后显著增加。这些结果表明，GM-CSF可能在将LCs / DCs募集到HPV转化的（癌前）子宫颈上皮中起重要作用，并可作为子宫颈（癌前）癌的一种新的免疫治疗方法。
