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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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1643421/full |
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| author | Xizi Li Xizi Li Siyuan Gao Chuchu Shan Chuchu Shan Qiling Zhang Qiling Zhang Ying Tan Ying Tan Ying Tan Xu Yu Xu Yu Xu Yu Jiangyi Yu Jiangyi Yu Jiangyi Yu |
| author_facet | Xizi Li Xizi Li Siyuan Gao Chuchu Shan Chuchu Shan Qiling Zhang Qiling Zhang Ying Tan Ying Tan Ying Tan Xu Yu Xu Yu Xu Yu Jiangyi Yu Jiangyi Yu Jiangyi Yu |
| author_sort | Xizi Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b8d4043a682b4cd3adb6ff27fdef1254 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-b8d4043a682b4cd3adb6ff27fdef12542025-08-20T03:59:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16434211643421Advances in PD-1/PD-L1 pathway inhibitors in the treatment of thyroid cancer: mechanisms and clinical therapeutic perspectivesXizi Li0Xizi Li1Siyuan Gao2Chuchu Shan3Chuchu Shan4Qiling Zhang5Qiling Zhang6Ying Tan7Ying Tan8Ying Tan9Xu Yu10Xu Yu11Xu Yu12Jiangyi Yu13Jiangyi Yu14Jiangyi Yu15Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, Nanjing, ChinaNanjing University of Chinese Medicine, Jiangsu, Nanjing, ChinaGuanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaAffiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, Nanjing, ChinaNanjing University of Chinese Medicine, Jiangsu, Nanjing, ChinaAffiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, Nanjing, ChinaNanjing University of Chinese Medicine, Jiangsu, Nanjing, ChinaAffiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, Nanjing, ChinaNanjing University of Chinese Medicine, Jiangsu, Nanjing, ChinaDepartment of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaAffiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, Nanjing, ChinaNanjing University of Chinese Medicine, Jiangsu, Nanjing, ChinaDepartment of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaAffiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu, Nanjing, ChinaNanjing University of Chinese Medicine, Jiangsu, Nanjing, ChinaDepartment of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaCancer 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1643421/fullthyroid cancerPD-1/PD-L1 inhibitorstargeted therapyimmunotherapyreview |
| spellingShingle | Xizi Li Xizi Li Siyuan Gao Chuchu Shan Chuchu Shan Qiling Zhang Qiling Zhang Ying Tan Ying Tan Ying Tan Xu Yu Xu Yu Xu Yu Jiangyi Yu Jiangyi Yu Jiangyi Yu Advances in PD-1/PD-L1 pathway inhibitors in the treatment of thyroid cancer: mechanisms and clinical therapeutic perspectives Frontiers in Immunology thyroid cancer PD-1/PD-L1 inhibitors targeted therapy immunotherapy review |
| title | Advances in PD-1/PD-L1 pathway inhibitors in the treatment of thyroid cancer: mechanisms and clinical therapeutic perspectives |
| title_full | Advances in PD-1/PD-L1 pathway inhibitors in the treatment of thyroid cancer: mechanisms and clinical therapeutic perspectives |
| title_fullStr | Advances in PD-1/PD-L1 pathway inhibitors in the treatment of thyroid cancer: mechanisms and clinical therapeutic perspectives |
| title_full_unstemmed | Advances in PD-1/PD-L1 pathway inhibitors in the treatment of thyroid cancer: mechanisms and clinical therapeutic perspectives |
| title_short | Advances in PD-1/PD-L1 pathway inhibitors in the treatment of thyroid cancer: mechanisms and clinical therapeutic perspectives |
| title_sort | advances in pd 1 pd l1 pathway inhibitors in the treatment of thyroid cancer mechanisms and clinical therapeutic perspectives |
| topic | thyroid cancer PD-1/PD-L1 inhibitors targeted therapy immunotherapy review |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1643421/full |
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