Tumor-infiltrating lymphocytes, particularly the balance between CD8(+) T cells and CCR4(+) regulatory T cells, affect the survival of patients with oral squamous cell carcinoma

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010 May;109(5):744-52. doi: 10.1016/j.tripleo.2009.12.015. Epub 2010 Mar 29.


Objective: The objective of this study was to clarify the prognostic significance of tumor-infiltrating lymphocytes (TILs) in oral squamous cell carcinoma (OSCC); the present study analyzed various TIL-related parameters.

Study design: Immunohistochemistry was performed in 87 patients with OSCC for the following TIL-related parameters: nest-CD8(+) T cells, stromal CD8(+) T cells, CD4(+) T cells, total regulatory T cells (Tregs), CCR4(+) Tregs, ratio of nest CD8(+) T cells/CCR4(+) Tregs, and ratio of stromal CD8(+) T cells/CCR4(+) Tregs.

Results: In univariate analyses, the following parameters were associated with decreased survival: few nest- and stromal CD8(+) T cells and more stromal CCR4(+) Tregs, but not total Tregs. Low ratios of nest and stromal CD8(+) T cell/CCR4(+) Treg were associated with worse survival. In multivariate analysis, the stromal CD8(+) T cell/CCR4(+) Treg ratio was an independent prognostic factor.

Conclusion: Host immune responses in the stroma of OSCC affect the survival of the patients. The in situ balance between effector T cells and regulatory T cells is the most important factor predicting survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / surgery
  • Female
  • Follow-Up Studies
  • Forkhead Transcription Factors / analysis
  • Gingival Neoplasms / immunology
  • Gingival Neoplasms / pathology
  • Gingival Neoplasms / surgery
  • Humans
  • Immunophenotyping
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • Mouth Neoplasms / immunology
  • Mouth Neoplasms / pathology*
  • Mouth Neoplasms / surgery
  • Neoplasm Staging
  • Prognosis
  • Receptors, CCR4 / immunology*
  • Retrospective Studies
  • Survival Rate
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Tongue Neoplasms / immunology
  • Tongue Neoplasms / pathology
  • Tongue Neoplasms / surgery


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Receptors, CCR4