Thomas D W, Matthews J B, Patel V, Game S M, Prime S S
Department of Oral Medicine, Pathology & Microbiology, University of Bristol, England.
J Oral Pathol Med. 1995 Jan;24(1):23-31. doi: 10.1111/j.1600-0714.1995.tb01125.x.
This study characterised the nature of the local cellular immune responses associated with an inbred animal model of oral carcinogenesis. Inbred F344 rats developed moderately- to well-differentiated primary oral squamous cell carcinomas (SCC) after treatment with the carcinogen 4-nitroquinoline N-oxide (4-NQO) in vivo for 5-6 months. The inflammatory cell infiltrate associated with the primary tumours was predominantly of the macrophage lineage (CD45+, Ia+) and contained smaller numbers of CD8+ cells (NK cells, cytotoxic/suppressor T cells), CD5+ cells (T cells) and CD25+ cells (activated cells; T and NK cells). Keratinocyte cell lines were established from three lingual and one palatal SCC. By contrast to normal keratinocytes, tumour-derived cell lines were immortal and independent of 3T3 fibroblast support. All of the tumour-derived cell lines were tumorigenic in athymic (nu/nu) mice and showed contrasting latent periods of tumour development and histological differentiation; normal keratinocyte grafts were non-tumorigenic in athymic mice. Three of four malignant cell lines formed well-differentiated tumours in syngeneic F344 rats; the tumours regressed after 10-14 days. Regressing grafts contained significantly larger numbers of NK cells (CD5-, CD8+) in the inflammatory cell infiltrate compared with that associated with primary tumours (p < 0.04). One malignant cell line and normal keratinocytes were non-tumorigenic in syngeneic hosts. The results demonstrate phenotypic variation in the cell-mediated immune responses associated with the actively growing primary SCC and the regressing tumours in syngeneic hosts and suggest that NK cells, possibly activated by local T cell responses, are important for tumour rejection in this model.
本研究对与口腔癌发生的近交系动物模型相关的局部细胞免疫反应的性质进行了表征。近交系F344大鼠在体内用致癌物4-硝基喹啉N-氧化物（4-NQO）处理5-6个月后，发生了中度至高度分化的原发性口腔鳞状细胞癌（SCC）。与原发性肿瘤相关的炎性细胞浸润主要是巨噬细胞谱系（CD45 +，Ia +），并且含有较少数量的CD8 +细胞（NK细胞、细胞毒性/抑制性T细胞）、CD5 +细胞（T细胞）和CD25 +细胞（活化细胞；T细胞和NK细胞）。从三个舌部和一个腭部SCC建立了角质形成细胞系。与正常角质形成细胞相比，肿瘤来源的细胞系是永生的，并且不依赖于3T3成纤维细胞的支持。所有肿瘤来源的细胞系在无胸腺（nu/nu）小鼠中具有致瘤性，并显示出不同的肿瘤发生潜伏期和组织学分化；正常角质形成细胞移植在无胸腺小鼠中不具有致瘤性。四个恶性细胞系中的三个在同基因F344大鼠中形成了高度分化的肿瘤；肿瘤在10-14天后消退。与原发性肿瘤相关的炎性细胞浸润相比，消退的移植物中NK细胞（CD5 -，CD8 +）的数量明显更多（p < 0.04）。一个恶性细胞系和正常角质形成细胞在同基因宿主中不具有致瘤性。结果表明，与同基因宿主中活跃生长的原发性SCC和消退的肿瘤相关的细胞介导免疫反应存在表型差异，并表明NK细胞可能由局部T细胞反应激活，在该模型中对肿瘤排斥很重要。
