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

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• 作者：Paramita Baruah^a ; ^b ; ^c ; ^{baruahpara@yahoo.co.in} ; Michael Lee^a ; Tunde Odutoye^a ; Peter Williamson^a ; Nicholas Hyde^b ; Juan Carlos Kaski^c ; Ingrid E. Dumitriu^c ; ^{i.dumitriu@sgul.ac.uk}
• 关键词：HNC ; head and neck cancer ; HPV ; human papilloma virus
• 刊名：Immunobiology
• 出版年：2012
• 期刊代码：3_01712985
• 类别：imm
• 出版时间：July, 2012
• 卷：217
• 期：7
• 页码：669-675
• 文件大小：845 K

摘要

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.