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免疫检查点分子在不同类型甲状腺癌中的高表达。

High Expression of Immune Checkpoint Molecules in Different Types of Thyroid Cancer.

机构信息

Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran AND Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Iran J Allergy Asthma Immunol. 2024 Oct 6;23(5):514-525. doi: 10.18502/ijaai.v23i5.16747.

DOI:10.18502/ijaai.v23i5.16747
PMID:39586745
Abstract

This study aimed to investigate the expression of programmed cell death protein-1 (PD-1) and its ligand (PD-L1) immune checkpoint molecules in thyroid carcinomas and determine their association with the clinicopathological characteristics of patients. Thyroid tissue specimens from 100 patients diagnosed with primary thyroid carcinomas including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC) were collected. Sections were prepared from formalin-fixed paraffin-embedded samples, and PD-1 and PD-L1 expressions were examined using immunohistochemistry. PD-1 was detected in tumor-infiltrating lymphocytes (TILs) in 88% of the patients and tumor cells in 28% of the patients with 10% in PTC, 5% in FTC, 5% in MTC, and 8% in ATC). PD-L1 was found in tumor cells and TILs in 30% and 79% of the patients, respectively. Moreover, a significant difference was observed in PD-1 and PD-L1 expression between tumor cells and TILs across different tumor types. However, their expression in tumor cells and TILs was significantly higher in ATC compared to other tumor types. Additionally, the expression of PD-1 and PD-L1 was significantly associated with an advanced stage, higher tumor size, tumor necrosis, and mitosis. A significant positive correlation was also observed between the expression of PD-1 and PD-L1 in tumor cells and TILs. The higher expression of PD-1 and PD-L1 may contribute to tumor progression. Therefore, combinational immunotherapy by these immune checkpoint inhibitors might be a promising strategy for clinical improvement in patients with thyroid cancer, especially those with ATC.

摘要

本研究旨在探讨程序性细胞死亡蛋白-1(PD-1)及其配体(PD-L1)免疫检查点分子在甲状腺癌中的表达,并确定其与患者临床病理特征的关系。收集了 100 例经组织学诊断为原发性甲状腺癌的患者(包括甲状腺乳头状癌(PTC)、滤泡状甲状腺癌(FTC)、甲状腺髓样癌(MTC)和间变性甲状腺癌(ATC))的甲状腺组织标本。从福尔马林固定石蜡包埋样本中制备切片,并用免疫组织化学检测 PD-1 和 PD-L1 的表达。在 88%的患者中,PD-1 在肿瘤浸润淋巴细胞(TILs)中检测到,在 28%的患者中在肿瘤细胞中检测到,其中 PTC 为 10%,FTC 为 5%,MTC 为 5%,ATC 为 8%。PD-L1 在肿瘤细胞和 TILs 中分别在 30%和 79%的患者中发现。此外,不同肿瘤类型之间在肿瘤细胞和 TILs 中 PD-1 和 PD-L1 的表达存在显著差异。然而,与其他肿瘤类型相比,在 ATC 中肿瘤细胞和 TILs 中 PD-1 和 PD-L1 的表达显著更高。此外,PD-1 和 PD-L1 的表达与晚期、较大的肿瘤大小、肿瘤坏死和有丝分裂显著相关。PD-1 和 PD-L1 在肿瘤细胞和 TILs 中的表达也存在显著的正相关。PD-1 和 PD-L1 的高表达可能有助于肿瘤的进展。因此,这些免疫检查点抑制剂的联合免疫疗法可能是改善甲状腺癌患者临床预后的一种有前途的策略,特别是对 ATC 患者。

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