Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients |
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Authors: | H-B Jie N Gildener-Leapman J Li R M Srivastava S P Gibson T L Whiteside R L Ferris |
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Institution: | 1.Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA;2.Department of Pharmacy, School of Medicine, Tsinghua University, Beijing, China;3.Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA;4.Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA;5.Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA |
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Abstract: | 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+CD25hi 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. |
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Keywords: | regulatory T cells checkpoint receptors tumour-infiltrating lymphocytes head and neck cancer |
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