Immune Co-inhibitory Receptors PD-1, CTLA-4, TIM-3, LAG-3, and TIGIT in Medullary Thyroid Cancers: A Large Cohort Study

作者：Xiao Shi, Cui-Wei Li, Licheng Tan, Shishuai Wen, Tian Liao, Yan Zhang, Tongzhen Chen, Ben Ma, Pengcheng Yu, Zhong‐Wu Lu, Ning Qu, Yu Wang, Yu Wang, Rong-Liang Shi, Yu-Long Wang, Yu-Long Wang, Qinghai Ji, Wenjun Wei · 发表于：The Journal of Clinical Endocrinology & Metabolism · 年份：2020 · DOI：10.1210/clinem/dgaa701 · 被引用次数：93 · 研究领域：Cancer Immunotherapy and Biomarkers、Thyroid Cancer Diagnosis and Treatment、Radiopharmaceutical Chemistry and Applications

CONTEXT: Programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), and T-cell immunoglobulin and ITIM domain (TIGIT) are considered major immune co-inhibitory receptors (CIRs) and the most promising immunotherapeutic targets in cancer treatment, but they are largely unexplored in medullary thyroid carcinoma (MTC). OBJECTIVE: We aimed to provide the first evidence regarding the expression profiles and clinical significance of CIRs in a large cohort of MTC patients. DESIGN AND PATIENTS: In total, 200 MTC patients who received initial surgery in our hospital were included. Immunohistochemistry was performed to evaluate CIR expressions in tissue microarrays (TMAs). Combined with the results of our previous programmed cell death ligand-1 (PD-L1) study, clinicopathologic and prognostic correlations of these proteins were retrospectively analyzed. RESULTS: TIM-3, PD-1, CTLA-4, LAG-3, and TIGIT positivity was detected in 96 (48.0%), 27 (13.5%), 25 (12.5%), 6 (3.0%), and 6 (3.0%) patients, respectively, in whom TIM-3, PD-1, and CTLA-4 expressions were positively correlated. Log-rank tests and multivariate Cox analyses both indicated that TIM-3, CTLA-4 expression, and PD-1/PD-L1 coexpression were associated with worse structural recurrence-free survival. In addition, among 20 patients who developed advanced disease during follow-up, 12 (60%) showed TIM-3 positivit...