The Journal of clinical endocrinology and metabolism · 2017
Epitope-Specific Antitumor Immunity Suppresses Tumor Spread in Papillary Thyroid Cancer.
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Ehlers Margret, Kuebart Anne, Hautzel Hubertus, Enczmann Juergen, Reis Anna-Carinna, Haase Matthias, Allelein Stephanie, Dringenberg Till, Schmid Christine, Schott Matthias
Аннотация
CONTEXT: Papillary thyroid cancer (PTC) is characterized by a lymphocytic infiltration. PTC patients with lymphocytic infiltration may have a better clinical outcome.
OBJECTIVE: Characterization of tumor epitope-specific immunity and correlation analyses with the clinical outcome.
PATIENTS: 150 PTC patients; 40 Hashimoto thyroiditis (HT) patients; 21 healthy controls; 27,239 healthy whites (for HLA typing).
MAIN OUTCOME MEASURES: 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.
RESULTS: 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.
CONCLUSION: 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.
OBJECTIVE: Characterization of tumor epitope-specific immunity and correlation analyses with the clinical outcome.
PATIENTS: 150 PTC patients; 40 Hashimoto thyroiditis (HT) patients; 21 healthy controls; 27,239 healthy whites (for HLA typing).
MAIN OUTCOME MEASURES: 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.
RESULTS: 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.
CONCLUSION: 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.
Предметные рубрики MeSH
AdultAgedAged, 80 and overAntigens, NeoplasmCD8-Positive T-LymphocytesCarcinomaCarcinoma, PapillaryCase-Control StudiesEpitopesEpitopes, T-LymphocyteFemaleHashimoto DiseaseHistocompatibility Antigens Class IIHistocompatibility TestingHumansImmunity, CellularLymphatic MetastasisLymphocytes, Tumor-InfiltratingMaleMiddle AgedPrognosisT-Lymphocyte SubsetsThyroid Cancer, PapillaryThyroid NeoplasmsYoung Adult