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Papillary Thyroid Carcinoma with Terminal Immune Exhaustion Phenotype Correlates with Increased Risk of Lymph Node Metastasis: An Exploratory Study Combining Flow Cytometry and TCGA

Sep 2026 · Cancers · Vol 18, pp. 2873 · 0 citations · 33 references
Medicine

TL;DR

It was found that LNM-positive PTC exhibited a terminal immune exhaustion phenotype characterized by enrichment of PD-1hiTIM-3+ CD8+ T cells and regulatory T cells and regulatory T cells, alongside elevated pro-inflammatory cytokines.

Abstract

Simple Summary Papillary thyroid carcinoma (PTC) frequently metastasizes to lymph nodes, yet reliable preoperative biomarkers are lacking. This study investigated the immune landscape of PTC prone to lymph node metastasis (LNM) using flow cytometry, immunohistochemistry, and cytokine profiling, complemented by TCGA transcriptomic analysis. We found that LNM-positive PTC exhibited a terminal immune exhaustion phenotype characterized by enrichment of PD-1hiTIM-3+ CD8+ T cells and regulatory T cells, alongside elevated pro-inflammatory cytokines. TCGA data further supported the association between terminal exhaustion signatures and advanced disease. Our findings offer new immune-related markers for risk evaluation and provide insights for developing combined immunotherapy for high-risk patients, which may help other researchers to design further clinical and experimental studies.

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