Advances in PD-1/PD-L1 pathway inhibitors in the treatment of thyroid cancer: mechanisms and clinical therapeutic perspectives

Advances in PD-1/PD-L1 pathway inhibitors in the treatment of thyroid cancer: mechanisms and clinical therapeutic perspectives

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 (I...

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Bibliographic Details
Main Authors: Xizi Li, Siyuan Gao, Chuchu Shan, Qiling Zhang, Ying Tan, Xu Yu, Jiangyi Yu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
Subjects:
thyroid cancer
PD-1/PD-L1 inhibitors
targeted therapy
immunotherapy
review
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1643421/full
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Summary: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.
ISSN:1664-3224

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