Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Virchows Arch. 2018 May;472(5):779-787. doi: 10.1007/s00428-018-2357-6. Epub 2018 Apr 12.
Immune checkpoint inhibitor therapies targeting PD-L1/PD-1 have been shown to be effective in treating several types of human cancer. In papillary thyroid carcinoma (PTC), little is known about the expression of PD-L1/PD-1 in the tumor microenvironment or its potential correlation with BRAF V600E mutation status. In this study, we examined the expression of PD-L1, PD-1, and BRAF V600E in PTC by immunohistochemistry and investigated the clinical significance of expression status. We studied the expression of PD-L1, PD-1, and BRAF V600E by immunohistochemical staining in 110 cases of PTC with a diameter > 1 cm. Cases with a background of chronic lymphocytic thyroiditis (CLT) were excluded, as differentiating lymphocytes in the context of CLT from tumor-infiltrating lymphocytes (TILs) is difficult. We classified PD-L1+/PD-1+ expression as type 1 (41%), PD-L1-/PD-1- as type 2 (17%), PD-L1+/PD-1- as type 3 (5%), and PD-L1-/PD-1+ as type 4 (37%). Significant correlations were found between expression of BRAF V600E and that of PD-L1 and PD-1. The positive correlation observed between expression of BRAF V600E and PD-L1/PD-1 suggests that immunotherapies targeting PD-L1/PD-1 might be effective for PTC patients with the BRAF V600E mutation, which are refractory to radioiodine therapy.
免疫检查点抑制剂靶向 PD-L1/PD-1 的治疗已被证明在治疗多种类型的人类癌症方面有效。在甲状腺乳头状癌 (PTC) 中,肿瘤微环境中 PD-L1/PD-1 的表达及其与 BRAF V600E 突变状态的潜在相关性知之甚少。在这项研究中,我们通过免疫组织化学检查了 PTC 中 PD-L1、PD-1 和 BRAF V600E 的表达,并研究了表达状态的临床意义。我们通过免疫组织化学染色研究了 110 例直径 > 1cm 的 PTC 中 PD-L1、PD-1 和 BRAF V600E 的表达。排除了有慢性淋巴细胞性甲状腺炎 (CLT) 背景的病例,因为在 CLT 背景下区分淋巴细胞与肿瘤浸润淋巴细胞 (TILs) 很困难。我们将 PD-L1+/PD-1+表达分类为 1 型 (41%)、PD-L1-/PD-1-为 2 型 (17%)、PD-L1+/PD-1-为 3 型 (5%)和 PD-L1-/PD-1+为 4 型 (37%)。BRAF V600E 的表达与 PD-L1 和 PD-1 的表达之间存在显著相关性。BRAF V600E 表达与 PD-L1/PD-1 表达之间观察到的正相关表明,针对 PD-L1/PD-1 的免疫疗法可能对放射性碘治疗耐药的 BRAF V600E 突变型 PTC 患者有效。