Decreased levels of alternative co-stimulatory receptors OX40 and 4-1BB characterise T cells from head and neck cancer patients.
OBJECTIVE
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.
Department of ENT, St. George's Hospital NHS Trust, London, UK. baruahpara@yahoo.co.in
Paramita
P
Baruah
Michael
M
Lee
Tunde
T
Odutoye
Peter
P
Williamson
Nicholas
N
Hyde
Juan Carlos
JC
Kaski
Ingrid E
IE
Dumitriu
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology; D002277:Carcinoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000276:immunology; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009367:Neoplasm Staging; D009975:Orthomyxoviridae / Q000276:immunology; D027383:Papillomaviridae / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D053262:Receptors, OX40 / Q000235:genetics* / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000235:genetics* / Q000276:immunology
D060908:CTLA-4 Antigen; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011948:Receptors, Antigen, T-Cell; D053262:Receptors, OX40; C505716:TNFRSF4 protein, human; C505714:TNFRSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9