Comparative Analysis of Tumor-Infiltrating Lymphocytes in a Syngeneic Mouse Model of Oral Cancer
Comparative Analysis of Tumor-Infiltrating Lymphocytes in a Syngeneic Mouse Model of Oral Cancer
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DOI：
10.1177/0194599812442037
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发表时间：
2012-09-01
影响因子：
3.4
通讯作者：
Uppaluri, Ravindra
中科院分区：
文献类型：
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作者：
Judd, Nancy P.;Allen, Clint T.;Uppaluri, Ravindra
目标。目的：对新建立的C57BL/6背景型小鼠口腔癌（MOC）模型中浸润免疫细胞进行比较分析。研究设计/设置。学术医疗中心的科学研究。方法。使用致癌物诱导的肿瘤发生、组织培养、细胞系移植和流式细胞术分析技术。此前，作者建立了一系列细胞系模型，当移植到免疫功能正常的小鼠体内时，这些模型显示出两种生长表型。他们现在表明，moc1产生的肿瘤的惰性生长模式与基线和可诱导的主要组织相容性复合体I类表达增加以及CD8(+) t细胞浸润到肿瘤微环境增加有关。相反，moc2产生的肿瘤的侵袭性和转移模式降低了基础和诱导型I类表达，并与FOXP3(+)CD4（+）调节性t细胞浸润有关。这些FOXP3（+）调节细胞在靶向单克隆抗体治疗后原发肿瘤生长延迟，进一步表明这些免疫细胞参与了mo2c的侵袭性表型。这些数据验证了在人类头颈癌中发现的关键浸润免疫细胞的平行发现，使这个新开发的同基因模型成为继续解剖头颈癌肿瘤-宿主相互作用的关键平台。
Objective. To perform a comparative analysis of infiltrating immune cells in a newly developed C57BL/6 background syngeneic transplantable mouse oral cancer (MOC) model.Study Design/Setting. Scientific study in an academic medical center.Methods. Use of carcinogen-induced tumorigenesis, tissue culture, cell line transplantation, and flow cytometric analysis techniques.Results. Previously, the authors established a series of cell line models that displayed dichotomous growth phenotypes when transplanted into immunocompetent mice. They now show that the indolent growth pattern of the MOC1-generated tumors is associated with increased baseline and inducible major histocompatibility complex class I expression and increased CD8(+) T-cell infiltration into the tumor microenvironment. Conversely, the aggressive and metastatic pattern of MOC2-generated tumors has decreased basal and inducible class I expression and is associated with FOXP3(+)CD4(+) regulatory T-cell infiltration. Delayed primary tumor growth after targeted monoclonal antibody therapy of these FOXP3(+) regulatory cells further suggests that these immune cells contribute to the aggressive phenotype of MOC2.Conclusion. These data validate that key infiltrating immune cells identified here parallel findings in human head and neck cancer, making this newly developed syngeneic model a critical platform for the continued dissection of tumor-host interactions in head and neck cancer.