In:
The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 102, No. 7 ( 2017-07-01), p. 2154-2161
Abstract:
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 & lt; 0.005 and P & lt; 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 & lt; 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 & lt; 0.05; HLA-DQB1*02: RR, 3.692; 95% CI, 1.102 to 12.38; P & lt; 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.
Type of Medium:
Online Resource
ISSN:
0021-972X
,
1945-7197
DOI:
10.1210/jc.2016-2469
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2017
detail.hit.zdb_id:
2026217-6
