Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine and School of Medicine, Seoul, Korea.
Thyroid. 2021 Jan;31(1):61-67. doi: 10.1089/thy.2020.0312. Epub 2020 Jul 28.
Advanced thyroid cancers, including differentiated thyroid carcinoma (DTC) with distant metastasis, and anaplastic thyroid carcinoma (ATC), are associated with poor clinical outcomes and limited treatment options. This study aimed to determine the immune profiles of advanced thyroid cancers using fluorescent multiplex immunohistochemistry (F-MIHC) and multispectral imaging (MSI). Twenty-eight tissue samples were collected from 12 patients who had DTC with distant metastasis and from 16 with ATC. The samples were assessed using F-MIHC and MSI with antibodies against the cell surface molecules, cluster of differentiation (CD)4, CD8, programmed cell death-1 (PD-1), PD ligand 1 (PD-L1), forkhead box protein 3, and cytokeratin (CK). The expression of PD-L1 was evaluated using tumor proportion score (TPS) and combined positive score (CPS). Significantly, more PD-L1-positive tumor cells (CKPD-L1) per mm were found in ATC samples than in DTC samples (183.5 vs. 0.03, < 0.001). Lymphocyte infiltration was significantly increased in ATC compared with DTC, with significantly more PD-L1- or PD-1-positive lymphocytes in ATC samples than in DTC samples. The TPS and CPS for PD-L1 expression were negative in all DTC samples but positive in 81% and 94% of ATC samples, respectively. Immune profiling revealed significant differences between advanced DTC and ATC, particularly in terms of PD-L1 expression and lymphocyte infiltration. Therefore, immune profiling using F-MIHC and MSI can provide invaluable information regarding tumor microenvironments, which could help select candidates for immunotherapy.
晚期甲状腺癌，包括伴有远处转移的分化型甲状腺癌（DTC）和间变性甲状腺癌（ATC），临床结局较差，治疗选择有限。本研究旨在通过荧光多重免疫组化（F-MIHC）和多光谱成像（MSI）来确定晚期甲状腺癌的免疫特征。 从 12 例伴有远处转移的 DTC 患者和 16 例 ATC 患者中收集了 28 个组织样本。使用针对细胞表面分子、分化簇（CD）4、CD8、程序性细胞死亡-1（PD-1）、PD 配体 1（PD-L1）、叉头框蛋白 3 和细胞角蛋白（CK）的 F-MIHC 和 MSI 评估样本。使用肿瘤比例评分（TPS）和联合阳性评分（CPS）评估 PD-L1 的表达。 与 DTC 样本相比，ATC 样本中每毫米 PD-L1 阳性肿瘤细胞（CKPD-L1）的数量明显更多（183.5 与 0.03， < 0.001）。与 DTC 相比，ATC 中的淋巴细胞浸润显著增加，ATC 样本中 PD-L1 或 PD-1 阳性淋巴细胞的数量明显多于 DTC 样本。所有 DTC 样本的 PD-L1 表达 TPS 和 CPS 均为阴性，但分别有 81%和 94%的 ATC 样本为阳性。 免疫分析显示晚期 DTC 和 ATC 之间存在显著差异，特别是在 PD-L1 表达和淋巴细胞浸润方面。因此，使用 F-MIHC 和 MSI 进行免疫分析可以提供有关肿瘤微环境的宝贵信息，这有助于选择免疫治疗候选者。
