Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients

Br J Cancer. 2013 Nov 12;109(10):2629-35. doi: 10.1038/bjc.2013.645. Epub 2013 Oct 29.


Background: Although regulatory T cells (Treg) are highly enriched in human tumours compared with peripheral blood, expression of the immune-checkpoint receptors, immunosuppressive molecules and function of Treg in these two sites remains undefined.

Methods: Tumour-infiltrating lymphocytes and peripheral blood lymphocytes were isolated from a cohort of head and neck squamous cell carcinoma (HNSCC) patients. The immunosuppressive phenotypes and function of intratumoral Treg were compared with those of peripheral blood Treg.

Results: The frequency of immune-checkpoint receptor-positive cells was higher on intratumoral FOXP3(+)CD25(hi) Treg compared with circulating Treg (CTLA-4, P=0.002; TIM-3, P=0.002 and PD-1, P=0.002). Immunosuppressive effector molecules, LAP and ectonucleotidase CD39 were also upregulated on intratumoral FOXP3(+) Treg (P=0.002 and P=0.004, respectively). CTLA-4 and CD39 were co-expressed on the majority of intratumoral FOXP3(+)CD4(+) Treg, suggesting that these molecules have a key role in regulatory functions of these cells in situ. Notably, intratumoral Treg exhibited more potently immunosuppressive activity than circulating Treg.

Conclusion: These results indicate that intratumoral Treg are more immunosuppressive than circulating Treg and CTLA-4 and CD39 expressed can be potential target molecules to inhibit suppressive activities of intratumoral Treg in situ.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / metabolism
  • Apyrase / metabolism
  • CTLA-4 Antigen / metabolism
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / metabolism
  • Cytokines / metabolism
  • Female
  • Head and Neck Neoplasms / blood
  • Head and Neck Neoplasms / immunology*
  • Head and Neck Neoplasms / metabolism
  • Humans
  • Immune Tolerance / immunology
  • Immunosuppressive Agents / metabolism*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Squamous Cell Carcinoma of Head and Neck
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / physiology*


  • Antigens, CD
  • CTLA-4 Antigen
  • Cytokines
  • Immunosuppressive Agents
  • Apyrase
  • CD39 antigen