title: Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients.
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(+)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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: H-B
authors.initials: HB
authors.lastname: Jie
authors.forename: N
authors.initials: N
authors.lastname: Gildener-Leapman
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: R M
authors.initials: RM
authors.lastname: Srivastava
authors.forename: S P
authors.initials: SP
authors.lastname: Gibson
authors.forename: T L
authors.initials: TL
authors.lastname: Whiteside
authors.forename: R L
authors.initials: RL
authors.lastname: Ferris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D001081:Apyrase / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007166:Immunosuppressive Agents / Q000378:metabolism*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000077195:Squamous Cell Carcinoma of Head and Neck; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; D016207:Cytokines; D007166:Immunosuppressive Agents; D001081:Apyrase; C067869:CD39 antigen