Comparative Analysis of Tumor-Infiltrating Lymphocytes in a Syngeneic Mouse Model of Oral Cancer

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.