Comparative analysis of tumor-infiltrating lymphocytes in a syngeneic mouse model of oral cancer

Otolaryngol Head Neck Surg. 2012 Sep;147(3):493-500. doi: 10.1177/0194599812442037. Epub 2012 Mar 19.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics
  • Disease Models, Animal*
  • Forkhead Transcription Factors / genetics
  • Gene Expression Regulation, Neoplastic / physiology
  • Histocompatibility Antigens Class I / analysis
  • Histocompatibility Antigens Class I / genetics
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / immunology
  • Mouth Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • Phenotype
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology
  • Transplantation, Isogeneic


  • Antibodies, Monoclonal
  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Histocompatibility Antigens Class I
  • Rag2 protein, mouse