Decreased levels of alternative co-stimulatory receptors OX40 and 4-1BB characterise T cells from head and neck cancer patients

Immunobiology. 2012 Jul;217(7):669-75. doi: 10.1016/j.imbio.2011.11.005. Epub 2011 Nov 22.

Abstract

Background and aim: Head and neck cancers (HNC) are aggressive tumours. Tumour-specific T cells are frequently identified in patients with cancer, although they fail to control tumour progression. A family of proteins called co-stimulatory receptors regulate the function of T cells and may account for T cell dysfunction in cancer. Our aim was to characterise co-stimulatory receptors on T cells in HNC patients to identify novel targets for immunotherapy.

Methods: Peripheral blood mononuclear cells were isolated from HNC patients and healthy controls and the expression of co-stimulatory (OX40, 4-1BB, ICOS) and co-inhibitory (CTLA-4, PD1) receptors was analysed on CD4(+) and CD8(+) T cells using flow cytometry.

Results: We found that the levels of co-stimulatory receptors OX40 and 4-1BB were significantly lower on CD4(+) T cells from HNC patients. This was more pronounced in locally advanced tumours (T3/T4) compared to early carcinomas (T1/T2). PD-1 levels were higher on CD8(+) T cells in HNC patients compared to controls. Human papilloma virus (HPV)-specific CD8(+) T cells appeared to be more affected than Influenza-specific T cells.

Conclusions: Our results indicate that expression of co-stimulatory receptors on T cells from HNC patients is imbalanced with a preponderance of inhibitory signals, and reduction of stimulatory signals, especially in advanced disease. Restoring this balance could improve T cell therapy outcomes in HNC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • CTLA-4 Antigen / genetics
  • CTLA-4 Antigen / immunology
  • Carcinoma / genetics*
  • Carcinoma / immunology
  • Carcinoma / pathology
  • Case-Control Studies
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / pathology
  • Humans
  • Inducible T-Cell Co-Stimulator Protein / genetics
  • Inducible T-Cell Co-Stimulator Protein / immunology
  • Influenza, Human / genetics
  • Influenza, Human / immunology
  • Influenza, Human / pathology
  • Neoplasm Staging
  • Orthomyxoviridae / immunology
  • Papillomaviridae / immunology
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, OX40 / genetics*
  • Receptors, OX40 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / genetics*
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology

Substances

  • CTLA-4 Antigen
  • ICOS protein, human
  • Inducible T-Cell Co-Stimulator Protein
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell
  • Receptors, OX40
  • TNFRSF4 protein, human
  • TNFRSF9 protein, human
  • Tumor Necrosis Factor Receptor Superfamily, Member 9