Li Xizi, Gao Siyuan, Shan Chuchu, Zhang Qiling, Tan Ying, Yu Xu, Yu Jiangyi
Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, Nanjing, China.
Nanjing University of Chinese Medicine, Jiangsu, Nanjing, China.
Front Immunol. 2025 Aug 8;16:1643421. doi: 10.3389/fimmu.2025.1643421. eCollection 2025.
Cancer of the thyroid is a endocrine cancer. Although most patients achieve favorable outcomes with surgical resection, radioactive iodine (RAI) ablation, and thyroid-stimulating hormone (TSH) suppression therapy, a subset progresses to advanced or refractory disease. Immune checkpoint inhibitors (ICIs) blocking the PD-1/PD-L1 pathway reactivate T cells, enabling them to identify and eradicate malignant cells, thus reinstating immune surveillance against tumors. This review examines PD-L1 (Programmed Death-Ligand 1) expression in thyroid cancer, exploring its underlying regulatory mechanisms. It also discusses recent advances in PD-1/PD-L1 immune checkpoint inhibition (ICI) therapy. Furthermore, the review highlights regulatory pathways modulating PD-1/PD-L1 expression, including the mTOR pathway, androgen receptor (AR), and the CKS1B/STAT3 pathway. Notably, it summarizes recent clinical developments, such as combination regimens pairing PD-L1 blockade with mutation-targeted therapies, for which the median OS of the targeted combination therapy group was 14.7 months. This therapy has achieved the longest median OS for anaplastic thyroid carcinoma (ATC) patients so far. Additionally, the review examines innovative treatment modalities, offering a thorough synthesis of the existing state and emerging trends in PD-1/PD-L1 immunotherapies.
甲状腺癌是一种内分泌癌。尽管大多数患者通过手术切除、放射性碘（RAI）消融和促甲状腺激素（TSH）抑制疗法可取得良好疗效，但仍有一部分患者会进展为晚期或难治性疾病。阻断PD-1/PD-L1通路的免疫检查点抑制剂（ICIs）可重新激活T细胞，使其能够识别并根除恶性细胞，从而恢复对肿瘤的免疫监视。本综述研究了甲状腺癌中PD-L1（程序性死亡配体1）的表达情况，探讨其潜在的调控机制。还讨论了PD-1/PD-L1免疫检查点抑制（ICI）疗法的最新进展。此外，该综述重点介绍了调节PD-1/PD-L1表达的调控途径，包括mTOR通路、雄激素受体（AR）和CKS1B/STAT3通路。值得注意的是，它总结了近期的临床进展，如将PD-L1阻断与靶向突变疗法相结合的联合治疗方案，靶向联合治疗组的中位总生存期为14.7个月。该疗法是目前为止间变性甲状腺癌（ATC）患者最长的中位总生存期。此外，该综述还研究了创新的治疗方式，全面综合了PD-1/PD-L1免疫疗法的现有状况和新趋势。
