该研究通过分析 City of Hope PTC 患者样本的免疫特征并将其与 TCGA 数据库中提供的甲状腺数据集进行比较，总结了免疫疗法治疗 BRAF 突变甲状腺乳头状癌 (PTC) 的潜在用途。 可用福尔马林固定的 PTC 病例鉴定出石蜡包埋的存档肿瘤组织。从肿瘤组织中提取 RNA 并通过 NanoString 进行分析，以评估其免疫基因表达谱。免疫组织化学用于测定免疫抑制基因的表达和肿瘤组织中的淋巴细胞浸润。采用甲状腺癌细胞系（MDA-T32、MDA-T68、MDA-T85和MDA-T120）来确定BRAF抑制与CD274表达之间的相关性。研究发现，具有BRAF突变的PTC病例具有更高的免疫表达检查点标记物 CD274 和 CTLA4，以及高级肿瘤浸润淋巴细胞，特别是 CD4 T 细胞。此外，该研究还发现了肿瘤细胞表达的免疫抑制标记物，如 CD73、CD276 和 CD200，这些标记物可以作为免疫治疗的目标。使用 PTC 细胞系的进一步实验得出这样的结论：CD274 表达与 BRAF 活性相关，并且 BRAF 抑制剂有可能与免疫疗法联合使用来治疗 PTC。这些发现表明，具有 BRAF 突变或高表达的 PTC 病例可能与 BRAF 活性相关。免疫热特征，可以从免疫治疗策略中受益。© 作者（或其雇主）2024。根据 CC BY-NC 允许重复使用。禁止商业再利用。请参阅权利和权限。英国医学杂志出版。

The study summarizes the potential use of immunotherapy for BRAF-mutated papillary thyroid cancer (PTC) by analyzing the immune profile of City of Hope PTC patient samples and comparing them to the thyroid dataset available in the TCGA database.PTC cases with available formalin-fixed paraffin-embedded archived tumor tissue were identified. RNA was extracted from the tumor tissue and analyzed by NanoString to evaluate their immune gene expression profile. Immunohistochemistry was used to determine the expression of immune suppressive genes and lymphocytic infiltration into the tumor tissue. Thyroid cancer cell lines (MDA-T32, MDA-T68, MDA-T85, and MDA-T120) were used to determine the correlation between the BRAF inhibition and CD274 expression.The study found that PTC cases with BRAF mutations had higher expression of immune checkpoint markers CD274 and CTLA4, as well as higher tumor-infiltrating lymphocytes, particularly CD4+T cells. Additionally, the study identified immunosuppressive markers expressed by tumor cells like CD73, CD276, and CD200 that could be targeted for immunotherapy. Further experiments using PTC cell lines lead to the conclusion that CD274 expression correlates with BRAF activity and that inhibitors of BRAF could potentially be used in combination with immunotherapy to treat PTC.These findings suggest that PTC cases with BRAF mutations or high expression may be correlated with an immune hot signature and could benefit from immunotherapeutic strategies.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.