{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:24:12Z","timestamp":1792686252181,"version":"4.5.0"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1643421","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T06:03:26Z","timestamp":1754633006000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Advances in PD-1\/PD-L1 pathway inhibitors in the treatment of thyroid cancer: mechanisms and clinical therapeutic perspectives"],"prefix":"10.3389","volume":"16","author":[{"given":"Xizi","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuchu","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.5998","article-title":"A review of thyroid cancer","volume":"331","author":"Beheshtirouy","year":"2024","journal-title":"Jama"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.35278","article-title":"The globocan 2022 cancer estimates: data sources, methods, and a snapshot of the cancer burden worldwide","volume":"156","author":"Filho","year":"2025","journal-title":"Int J Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.593479","article-title":"Signal pathway of estrogen and estrogen receptor in the development of thyroid cancer","volume":"11","author":"Liu","year":"2021","journal-title":"Front Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1530\/erc-24-0348","article-title":"Sexual dimorphism in thyroid cancer: evidence from preclinical studies","volume":"32","author":"Coperchini","year":"2025","journal-title":"Endocrine-related Cancer"},{"key":"B5","article-title":"Pd-1\/pd-L1 pathway: current researches in cancer","volume":"10","author":"Han","year":"2020","journal-title":"Am J Cancer Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1530\/erc-16-0421","article-title":"Comprehensive screening for pd-L1 expression in thyroid cancer","volume":"24","author":"Ahn","year":"2017","journal-title":"Endocrine-related Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.09.016","article-title":"Dysfunction of natural killer cells mediated by pd-1 and tim-3 pathway in anaplastic thyroid cancer","volume":"64","author":"Yin","year":"2018","journal-title":"Int Immunopharmacol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-12-195792","article-title":"Tumor antigen-specific cd8 T cells infiltrating the tumor express high levels of pd-1 and are functionally impaired","volume":"114","author":"Ahmadzadeh","year":"2009","journal-title":"Blood"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.10.013","article-title":"The transcription factor foxo1 sustains expression of the inhibitory receptor pd-1 and survival of antiviral cd8(+) T cells during chronic infection","volume":"41","author":"Staron","year":"2014","journal-title":"Immunity"},{"key":"B10","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s00251-017-1015-5","article-title":"Pd-1 and cancer: molecular mechanisms and polymorphisms","volume":"70","author":"Salmaninejad","year":"2018","journal-title":"Immunogenetics"},{"key":"B11","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s41073-019-0064-8","article-title":"Sanra-a scale for the quality assessment of narrative review articles","volume":"4","author":"Baethge","year":"2019","journal-title":"Res Integrity Peer Rev"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.03.031","article-title":"Programmed death - ligand 1 expression distinguishes invasive encapsulated follicular variant of papillary thyroid carcinoma from noninvasive follicular thyroid neoplasm with papillary-like nuclear features","volume":"18","author":"Fu","year":"2017","journal-title":"EBioMedicine"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0228","article-title":"Programmed death-ligand 1 expression in papillary thyroid cancer and its correlation with clinicopathologic factors and recurrence","volume":"27","author":"Shi","year":"2017","journal-title":"Thyroid: Off J Am Thyroid Assoc"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-4227","article-title":"Tumor-infiltrating T cells and the pd-1 checkpoint pathway in advanced differentiated and anaplastic thyroid cancer","volume":"101","author":"Bastman","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8698","article-title":"Programmed death-ligand 1 overexpression is a prognostic marker for aggressive papillary thyroid cancer and its variants","volume":"7","author":"Chowdhury","year":"2016","journal-title":"Oncotarget"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2014.0134","article-title":"Braf V600e in papillary thyroid carcinoma is associated with increased programmed death ligand 1 expression and suppressive immune cell infiltration","volume":"24","author":"Angell","year":"2014","journal-title":"Thyroid: Off J Am Thyroid Assoc"},{"key":"B17","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1007\/s12105-024-01618-5","article-title":"Chronic lymphocytic thyroiditis with oncocytic metaplasia influences pd-L1 expression in papillary thyroid carcinoma","volume":"18","author":"Santana","year":"2024","journal-title":"Head Neck Pathol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2147\/cmar.S392475","article-title":"Association of programmed death-ligand 1 expression with aggressive histological types of thyroid carcinoma","volume":"14","author":"Harahap","year":"2022","journal-title":"Cancer Manage Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2019.11.007","article-title":"Pd-L1 expression in papillary thyroid cancer with and without lymphocytic thyroiditis: A cross sectional study","volume":"52","author":"Fadia","year":"2020","journal-title":"Pathology"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.22224","article-title":"Pd-L1 and thyroid cytology: A possible diagnostic and prognostic marker","volume":"128","author":"Dell\u2019Aquila","year":"2020","journal-title":"Cancer Cytopathol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26083757","article-title":"Braf targeting across solid tumors: molecular aspects and clinical applications","volume":"26","author":"Mechahougui","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2024.0266","article-title":"Transcriptome of anaplastic thyroid cancer reveals two molecular subtypes with distinct tumor microenvironment and prognosis","volume":"35","author":"Byun","year":"2025","journal-title":"Thyroid: Off J Am Thyroid Assoc"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-018-2357-6","article-title":"In papillary thyroid carcinoma, expression by immunohistochemistry of braf V600e, pd-L1, and pd-1 is closely related","volume":"472","author":"Bai","year":"2018","journal-title":"Virchows Archiv: An Int J Pathol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0296-2","article-title":"Combinations of braf inhibitor and anti-pd-1\/pd-L1 antibody improve survival and tumour immunity in an immunocompetent model of orthotopic murine anaplastic thyroid cancer","volume":"119","author":"Gunda","year":"2018","journal-title":"Br J Cancer"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1178682","article-title":"Case report: complete response of an anaplastic thyroid carcinoma patient with nras Q61r\/braf D594n mutations to the triplet of dabrafenib, trametinib and pd-1 antibody","volume":"14","author":"Gui","year":"2023","journal-title":"Front Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.07.024","article-title":"Role of mirnas in tumor and endothelial cell interactions during tumor progression","volume":"60","author":"Orso","year":"2020","journal-title":"Semin Cancer Biol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1186\/s12885-022-09838-0","article-title":"The mir-199a-5p\/pd-L1 axis regulates cell proliferation, migration and invasion in follicular thyroid carcinoma","volume":"22","author":"Lin","year":"2022","journal-title":"BMC Cancer"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2022.104787","article-title":"The pi3k\/akt signaling pathway in cancer: molecular mechanisms and possible therapeutic interventions","volume":"127","author":"Khezri","year":"2022","journal-title":"Exp Mol Pathol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2024.114229","article-title":"Leptin and insulin synergize with pik3ca mutation to enhance pd-L1 mediated immunosuppression in thyroid cancer","volume":"442","author":"Wu","year":"2024","journal-title":"Exp Cell Res"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.12.009","article-title":"Acetylcholine promotes the self-renewal and immune escape of cd133+ Thyroid cancer cells through activation of cd133-akt pathway","volume":"471","author":"Wang","year":"2020","journal-title":"Cancer Lett"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2014.11.014","article-title":"Intrinsic and extrinsic control of expression of the immunoregulatory molecule pd-L1 in epithelial cells and squamous cell carcinoma","volume":"51","author":"Ritprajak","year":"2015","journal-title":"Oral Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2011.01438.x","article-title":"Everolimus is an active agent in medullary thyroid cancer: A clinical and in vitro study","volume":"16","author":"Faggiano","year":"2012","journal-title":"J Cell Mol Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0662","article-title":"Dual inhibition of mitogen-activated protein kinase kinase and mammalian target of rapamycin in differentiated and anaplastic thyroid cancer","volume":"94","author":"Jin","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112764","article-title":"Enhanced bypass of pd-L1 translation reduces the therapeutic response to mtor kinase inhibitors","volume":"42","author":"Cao","year":"2023","journal-title":"Cell Rep"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt379","article-title":"A multicenter, phase ii trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes","volume":"24","author":"Lim","year":"2013","journal-title":"Ann Oncol: Off J Eur Soc Med Oncol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15061665","article-title":"Clinical implications of mtor expression in papillary thyroid cancer-a systematic review","volume":"15","author":"Derwich","year":"2023","journal-title":"Cancers"},{"key":"B37","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/s41389-023-00496-w","article-title":"Nf-\u03bab signaling activation and roles in thyroid cancers: implication of map3k14\/nik","volume":"12","author":"Cormier","year":"2023","journal-title":"Oncogenesis"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2018.0775","article-title":"Risk for thyroid cancer recurrence is higher in men than in women independent of disease stage at presentation","volume":"30","author":"Zahedi","year":"2020","journal-title":"Thyroid: Off J Am Thyroid Assoc"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e15559","DOI":"10.1097\/md.0000000000015559","article-title":"Current trends in the features of male thyroid cancer: retrospective evaluation of their prognostic value","volume":"98","author":"Kim","year":"2019","journal-title":"Medicine"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2964(79)90291-3","article-title":"A prognostic index for thyroid carcinoma. A study of the E.O.R.T.C. Thyroid cancer cooperative group","volume":"15","author":"Byar","year":"1979","journal-title":"Eur J Cancer"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.663130","article-title":"Androgen activity is associated with pd-L1 downregulation in thyroid cancer","volume":"9","author":"O\u2019Connell","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"eabq2630","DOI":"10.1126\/sciimmunol.abq2630","article-title":"Androgen conspires with the cd8(+) T cell exhaustion program and contributes to sex bias in cancer","volume":"7","author":"Kwon","year":"2022","journal-title":"Sci Immunol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"e23565","DOI":"10.1002\/jcla.23565","article-title":"Cks1b promotes cell proliferation and invasion by activating stat3\/pd-L1 and phosphorylation of akt signaling in papillary thyroid carcinoma","volume":"35","author":"Wang","year":"2021","journal-title":"J Clin Lab Anal"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(16)30066-3","article-title":"Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (Keynote-012): an open-label, multicentre, phase 1b trial","volume":"17","author":"Seiwert","year":"2016","journal-title":"Lancet Oncol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/s12885-019-5380-3","article-title":"Safety and antitumor activity of the anti-pd-1 antibody pembrolizumab in patients with advanced, pd-L1-positive papillary or follicular thyroid cancer","volume":"19","author":"Mehnert","year":"2019","journal-title":"BMC Cancer"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34657","article-title":"Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 keynote-158 study","volume":"129","author":"Oh","year":"2023","journal-title":"Cancer"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1200\/jco.19.02727","article-title":"Pd-1 blockade in anaplastic thyroid carcinoma","volume":"38","author":"Capdevila","year":"2020","journal-title":"J Clin Oncol: Off J Am Soc Clin Oncol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2022.100419","article-title":"Phase ii multicohort study of atezolizumab monotherapy in multiple advanced solid cancers","volume":"7","author":"Tabernero","year":"2022","journal-title":"ESMO Open"},{"key":"B49","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1038\/nrc.2017.17","article-title":"Prospects for combining targeted and conventional cancer therapy with immunotherapy","volume":"17","author":"Gotwals","year":"2017","journal-title":"Nat Rev Cancer"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32041","article-title":"Anti-pd-1\/pd-L1 therapy augments lenvatinib\u2019s efficacy by favorably altering the immune microenvironment of murine anaplastic thyroid cancer","volume":"144","author":"Gunda","year":"2019","journal-title":"Int J Cancer"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-023-14031-z","article-title":"The efficacy and safety of surufatinib combined with anti pd-1 antibody toripalimab in neoadjuvant treatment of locally advanced differentiated thyroid cancer: A phase ii study","volume":"30","author":"Chen","year":"2023","journal-title":"Ann Surg Oncol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.4729","article-title":"Anti-programmed death ligand 1 plus targeted therapy in anaplastic thyroid carcinoma: A nonrandomized clinical trial","volume":"10","author":"Cabanillas","year":"2024","journal-title":"JAMA Oncol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"6085","DOI":"10.1200\/JCO.2022.40.16_suppl.6085","article-title":"A phase ii study to evaluate the efficacy and safety of camrelizumab plus famitinib in advanced or metastatic thyroid cancer","volume":"40","author":"Ji","year":"2022","journal-title":"J Clin Oncol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2023.0573","article-title":"Checkpoint inhibition in addition to dabrafenib\/trametinib for braf(V600e)-mutated anaplastic thyroid carcinoma","volume":"34","author":"Hamidi","year":"2024","journal-title":"Thyroid: Off J Am Thyroid Assoc"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0133","article-title":"Complete surgical resection following neoadjuvant dabrafenib plus trametinib in braf(V600e)-mutated anaplastic thyroid carcinoma","volume":"29","author":"Wang","year":"2019","journal-title":"Thyroid: Off J Am Thyroid Assoc"},{"key":"B56","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s13045-022-01325-0","article-title":"Immune checkpoint modulators in cancer immunotherapy: recent advances and emerging concepts","volume":"15","author":"Wang","year":"2022","journal-title":"J Hematol Oncol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.4019","article-title":"Dual immune checkpoint inhibition in patients with aggressive thyroid carcinoma: A phase 2 nonrandomized clinical trial","volume":"10","author":"Sehgal","year":"2024","journal-title":"JAMA Oncol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1177\/2050313x241313084","article-title":"Advanced anaplastic thyroid carcinoma with positive expression of pd-L1 response to immune checkpoint inhibitors: A case report","volume":"13","author":"Fan","year":"2025","journal-title":"SAGE Open Med Case Rep"},{"key":"B59","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.aace.2021.03.003","article-title":"Anaplastic thyroid cancer successfully treated with radiation and immunotherapy: A case report","volume":"7","author":"Yang","year":"2021","journal-title":"AACE Clin Case Rep"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1125226","article-title":"Radiotherapy combined with immunotherapy successfully treated one case of anaplastic thyroid cancer: A case report","volume":"13","author":"Xing","year":"2023","journal-title":"Front Oncol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"419","DOI":"10.4103\/0019-5154.160511","article-title":"Vorinostat-an overview","volume":"60","author":"Bubna","year":"2015","journal-title":"Indian J Dermatol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603463","article-title":"Cancer biology: mechanism of antitumour action of vorinostat (Suberoylanilide hydroxamic acid), a novel histone deacetylase inhibitor","volume":"95","author":"Richon","year":"2006","journal-title":"Br J Cancer"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2007.11.003","article-title":"Valproic acid as epigenetic cancer drug: preclinical, clinical and transcriptional effects on solid tumors","volume":"34","author":"Duenas-Gonzalez","year":"2008","journal-title":"Cancer Treat Rev"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-020-00834-y","article-title":"Hdac inhibition induces pd-L1 expression in a novel anaplastic thyroid cancer cell line","volume":"26","author":"Heged\u0171s","year":"2020","journal-title":"Pathol Oncol Res: POR"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-014-0091-8","article-title":"Progress in oncolytic virotherapy for the treatment of thyroid Malignant neoplasm","volume":"33","author":"Guan","year":"2014","journal-title":"J Exp Clin Cancer Res: CR"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.7314\/apjcp.2015.16.3.1241","article-title":"Treatment of human thyroid carcinoma cells with the G47delta oncolytic herpes simplex virus","volume":"16","author":"Wang","year":"2015","journal-title":"Asian Pacific J Cancer Prevention: APJCP"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000698","article-title":"Combining braf inhibition with oncolytic herpes simplex virus enhances the immune-mediated antitumor therapy of braf-mutant thyroid cancer","volume":"8","author":"Crespo-Rodriguez","year":"2020","journal-title":"J Immunother Cancer"},{"key":"B68","doi-asserted-by":"publisher","first-page":"e90064","DOI":"10.1172\/jci.insight.90064","article-title":"Longitudinal pet imaging demonstrates biphasic car T cell responses in survivors","volume":"1","author":"Vedvyas","year":"2016","journal-title":"JCI Insight"},{"key":"B69","doi-asserted-by":"publisher","first-page":"e970027","DOI":"10.4161\/21624011.2014.970027","article-title":"Chimeric antigen receptor T cells are vulnerable to immunosuppressive mechanisms present within the tumor microenvironment","volume":"3","author":"Beatty","year":"2014","journal-title":"Oncoimmunology"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-13-2627","article-title":"Multifactorial T-cell hypofunction that is reversible can limit the efficacy of chimeric antigen receptor-transduced human T cells in solid tumors","volume":"20","author":"Moon","year":"2014","journal-title":"Clin Cancer Res: An Off J Am Assoc Cancer Res"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0297-y","article-title":"Engineering strategies to overcome the current roadblocks in car T cell therapy","volume":"17","author":"Rafiq","year":"2020","journal-title":"Nat Rev Clin Oncol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-20-1523","article-title":"Pd1 blockade enhances icam1-directed car T therapeutic efficacy in advanced thyroid cancer","volume":"26","author":"Gray","year":"2020","journal-title":"Clin Cancer Res: An Off J Am Assoc Cancer Res"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.2174\/0118715303248000230922185110","article-title":"Network pharmacological analysis and experimental validation of the effects of silybin on proliferation, migration, and immunotherapy of papillary thyroid cancer","volume":"24","author":"Xie","year":"2024","journal-title":"Endocrine Metab Immune Disord Drug Targets"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2025.155898","article-title":"Curcumin enhances anti-tumor immunity in anaplastic thyroid carcinoma by elevating cd8+ T cell function and downregulating the akt\/mtorc1\/stat3\/pd-L1 axis","volume":"269","author":"Zheng","year":"2025","journal-title":"Pathol Res Pract"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1643421\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T06:03:27Z","timestamp":1754633007000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1643421\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,8]]},"references-count":74,"alternative-id":["10.3389\/fimmu.2025.1643421"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1643421","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,8]]},"article-number":"1643421"}}