title: Epitope-Specific Antitumor Immunity Suppresses Tumor Spread in Papillary Thyroid Cancer.
abstract: Papillary thyroid cancer (PTC) is characterized by a lymphocytic infiltration. PTC patients with lymphocytic infiltration may have a better clinical outcome.
  
  
  
  Characterization of tumor epitope-specific immunity and correlation analyses with the clinical outcome.
  
  
  
  150 PTC patients; 40 Hashimoto thyroiditis (HT) patients; 21 healthy controls; 27,239 healthy whites (for HLA typing).
  
  
  
  HLA class I restricted thyroperoxidase (TPO) and thyroglobulin (Tg) epitope-specific T cells (tetramer analyses), correlation analyses between HLA class II phenotypes, T cell immunity, and the clinical course.
  
  
  
  The frequency of TPO- and Tg-specific CD8+ T cells in PTC patients was largely increased compared with healthy controls (TPO and Tg, P < 0.005 and P < 0.005) and was similar to those in HT patients. HLA-DQB1*03-positive PTC patients had a significantly lower risk [risk ratio (RR), 0.170; 95% confidence interval (CI), 0.037 to 0.755; P < 0.05] and HLA-DRB1*03-positive and HLA-DQB1*02-positive PTC patients a significantly higher risk (HLA-DRB1*03: RR, 4.400; 95% CI, 1.378 to 14.05; P < 0.05; HLA-DQB1*02: RR, 3.692; 95% CI, 1.102 to 12.38; P < 0.05) for distant metastases, compared with patients with other haplotypes. HLA-DQB1*03-positive PTC patients revealed an increased responsiveness of tumor epitopes in vitro. These tumor epitope-specific CD8+ T cells were also found in lymph node metastases of HLA-DQB1*03-positive PTC patients.
  
  
  
  We demonstrate a tumor epitope-specific immunity in PTC patients and the protective role of HLA-DQB1*03 against metastatic spread. These results have direct implications for new treatment options with immune checkpoint inhibitors.
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany.
authors.forename: Margret
authors.initials: M
authors.lastname: Ehlers
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Kuebart
authors.affiliation: Clinic for Nuclear Medicine, University Hospital Duesseldorf, 40225 Duesseldorf, Germany.
authors.forename: Hubertus
authors.initials: H
authors.lastname: Hautzel
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics.
authors.forename: Juergen
authors.initials: J
authors.lastname: Enczmann
authors.affiliation: Institute of Pathology, Medical School, Heinrich Heine University, 40225 Duesseldorf, Germany.|Institute of Pathology, University Hospital of Essen, University of Duisburg - Essen, 45147 Essen, Germany.
authors.forename: Anna-Carinna
authors.initials: AC
authors.lastname: Reis
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Haase
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Allelein
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Dringenberg
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Schmid
authors.affiliation: Division for Specific Endocrinology, Medical Faculty, University of Duesseldorf, 40225 Duesseldorf, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schott
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology / Q000556:secondary; D002291:Carcinoma, Papillary; D016022:Case-Control Studies; D000939:Epitopes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D050031:Hashimoto Disease / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007111:Immunity, Cellular; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000276:immunology* / Q000473:pathology / Q000556:secondary; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II