{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:54:50Z","timestamp":1780084490663,"version":"3.54.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["National Natural Science Foundation of China , 82160570, 82060485, the Applied Basic Research Project of Qinghai Provincial Science and Technology Department(No.2019-ZJ-7091), the Student Innovation and Entrepreneurship Fund Program of Qinghai University affiliated Hospital (School of Clinical Medicine)( No.CXCY202303), the Youth and Middle-aged Research Fund Program of Affiliated Hospital of Qinghai University\uff08No.ASRF-2022-YB-12.\uff09, National Natural Science Foundation of China (82060485) , National Natural Science Foundation of China (82160570)"],"award-info":[{"award-number":["National Natural Science Foundation of China , 82160570, 82060485, the Applied Basic Research Project of Qinghai Provincial Science and Technology Department(No.2019-ZJ-7091), the Student Innovation and Entrepreneurship Fund Program of Qinghai University affiliated Hospital (School of Clinical Medicine)( No.CXCY202303), the Youth and Middle-aged Research Fund Program of Affiliated Hospital of Qinghai University\uff08No.ASRF-2022-YB-12.\uff09, National Natural Science Foundation of China (82060485) , National Natural Science Foundation of China (82160570)"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Molecularly targeted therapies and immunotherapy are increasingly being employed in the treatment of aggressive, recurrent thyroid cancer. Evidence from several studies indicates that a significant proportion of tumor patients derive limited benefit from immunotherapy as a monotherapy, with vascular abnormalities in solid tumors contributing to immune evasion. Numerous studies, both domestic and international, have assessed the efficacy of combining immune checkpoint inhibitors with antiangiogenic agents across various tumor types. These studies suggest that such combination therapies are effective in controlling disease progression and extending survival, among other outcomes. Nevertheless, further research is warranted to substantiate these findings and optimize treatment protocols.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study aims to describe a patient diagnosed with anaplastic thyroid carcinoma (ATC) combined with primary squamous cell carcinoma of the thyroid (PSCCT) and concurrent thyroid abscess. The patient experienced local recurrence and metastasis following surgical intervention, radiotherapy, and chemotherapy, and was found to be PD-1 negative. Disease progression was effectively controlled through combination therapy with anlotinib and tislelizumab. Additionally, a comprehensive review of the relevant literature was conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patient exhibited disease recurrence 8 months postoperatively, notwithstanding the administration of adjuvant radiotherapy and chemotherapy. The local recurrent mass demonstrated minimal reduction following 4 cycles of targeted therapy with anlotinib. However, subsequent treatment with a combination of anlotinib and tislelizumab resulted in a substantial reduction of the neck mass and enlarged cervical lymph nodes after 12 cycles. The patient tolerated the combination therapy well, experiencing no significant adverse effects aside from pronounced fatigue. Thus, the combination therapy with anlotinib and tislelizumab proved effective in controlling the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The management of postoperative recurrence of ATC-PSCCT presents significant challenges, as recurrent tumors typically demonstrate increased aggressiveness and resistance to pharmacological interventions, necessitating multimodal therapeutic approaches. Tislelizumab, an immune checkpoint inhibitor, may facilitate immune-mediated tumor clearance through the activation of various immune cells, including natural killer cells and macrophages. Despite the patient\u2019s PD-1 negativity, the combination of anlotinib and tislelizumab may exert synergistic effects through distinct mechanisms, thereby potentially enhancing therapeutic efficacy. The integration of a multi-targeted tyrosine kinase inhibitor within this combination therapy regimen warrants further investigation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1477954","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T07:10:07Z","timestamp":1742368207000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy of combined immunotherapy and targeted therapy in overcoming barriers to postoperative recurrence in squamous subtype anaplastic thyroid carcinoma with abscess: a case report and literature review"],"prefix":"10.3389","volume":"15","author":[{"given":"Shuyun","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijun","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2013.03.440","article-title":"Anaplastic thyroid cancer","volume":"49","author":"O\u2019Neill","year":"2013","journal-title":"Oral Oncol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s12022-022-09707-3","article-title":"Overview of the 2022 WHO classification of thyroid neoplasms","volume":"33","author":"Baloch","year":"2022","journal-title":"Endocr Pathol.2022;"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.2001.01207.x","article-title":"Primary squamous cell carcinoma of the thyroid gland: an entity with aggressive clinical behaviour and distinctive cytokeratin expression profiles","volume":"39","author":"Lam","year":"2001","journal-title":"Histopathology"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1177\/0194599817698436","article-title":"Primary squamous cell carcinoma of the thyroid: A population-based analysis","volume":"157","author":"Au","year":"2017","journal-title":"Otolaryngol Head Neck Surg"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2014.3.issue-5","article-title":"Primary squamous cell carcinomas in the thyroid gland: an individual participant data meta-analysis","volume":"3","author":"Cho","year":"2014","journal-title":"Cancer Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2324709618778709","DOI":"10.1177\/2324709618778709","article-title":"Thyroid abscess: challenges in diagnosis and management","volume":"6","author":"Yedla","year":"2018","journal-title":"J Investig Med High Impact Case Rep"},{"key":"B7","article-title":"Thyroid abscess as a clinical manifestation of papillary thyroid carcinoma","volume":"54","author":"Tarigan","year":"2022","journal-title":"Acta Med Indones"},{"key":"B8","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s13045-016-0332-8","article-title":"Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors","volume":"9","author":"Sun","year":"2016","journal-title":"J Hematol Oncol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1097\/PPO.0000000000000327","article-title":"Combinations of bevacizumab with cancer immunotherapy","volume":"24","author":"Chen","year":"2018","journal-title":"Cancer J"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.3362","article-title":"Evaluation of overall survival in patients with anaplastic thyroid carcinoma, 2000-2019","volume":"6","author":"Maniakas","year":"2020","journal-title":"JAMA Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1556\/650.2023.32858","article-title":"A pajzsmirigy primer laph\u00e1mcarcinom\u00e1ja [Primary squamous cell carcinoma of the thyroid gland]. the thyroid gland]","volume":"164","author":"L\u00e9vay","year":"2023","journal-title":"Orv Hetil"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s13193-016-0530-4","article-title":"Primary squamous cell carcinoma of thyroid - A rare Malignant goitre","volume":"7","author":"Shenoy","year":"2016","journal-title":"Indian J Surg Oncol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1916-0216-43-17","article-title":"Primary squamous cell of the thyroid-an abbreviated clinical presentation","volume":"43","author":"Lui","year":"2014","journal-title":"J Otolaryngol Head Neck Surg"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4132\/KoreanJPathol.2014.48.6.418","article-title":"Combined squamous cell carcinoma and follicular carcinoma of the thyroid","volume":"48","author":"Son","year":"2014","journal-title":"Korean J Pathol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"646209","DOI":"10.1155\/2015\/646209","article-title":"Giant thyroid abscess related to postpartum Brucella infection","volume":"2015","author":"Akdemir","year":"2015","journal-title":"Case Rep Infect Dis"},{"key":"B16","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1186\/s13046-020-01709-5","article-title":"The role of microenvironment in tumor angiogenesis","volume":"39","author":"Jiang","year":"2020","journal-title":"J Exp Clin Cancer Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s00424-016-1877-7","article-title":"Claudins in cancer: bench to bedside","volume":"469","author":"Osanai","year":"2017","journal-title":"Pflugers Arch"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/ddg.15333","article-title":"Squamous cell carcinoma mimicking inflammatory cysts or abscesses: Role of high-frequency sonography as supporting diagnostic tool","volume":"22","author":"Crisan","year":"2024","journal-title":"J Dtsch Dermatol Ges"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/jcu.20288","article-title":"Nonsurgical management of thyroid abscess with sonographically guided fine needle aspiration","volume":"35","author":"Ilyin","year":"2007","journal-title":"J Clin Ultrasound"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2020.0944","article-title":"2021 American thyroid association guidelines for management of patients with anaplastic thyroid cancer","volume":"31","author":"Bible","year":"2021","journal-title":"Thyroid"},{"key":"B21","doi-asserted-by":"publisher","first-page":"100668","DOI":"10.1016\/j.currproblcancer.2020.100668","article-title":"Rechallenge with dabrafenib plus trametinib in anaplastic thyroid cancer: A case report and review of literature","volume":"45","author":"Ar\u0131kan","year":"2021","journal-title":"Curr Probl Cancer"},{"key":"B22","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":"B23","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S305196","article-title":"A remarkable and durable response to sintilimab and anlotinib in the first-line treatment of an anaplastic thyroid carcinoma without targetable genomic alterations: A case report","volume":"14","author":"Gui","year":"2021","journal-title":"Onco Targets Ther"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2017-0096","article-title":"Exceptional response with immunotherapy in a patient with anaplastic thyroid cancer","volume":"22","author":"Kollipara","year":"2017","journal-title":"Oncologist"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2020.0322","article-title":"Combination of lenvatinib and pembrolizumab is an effective treatment option for anaplastic and poorly differentiated thyroid carcinoma","volume":"31","author":"Dierks","year":"2021","journal-title":"Thyroid"},{"key":"B26","doi-asserted-by":"publisher","first-page":"bcr2016217143","DOI":"10.1136\/bcr-2016-217143","article-title":"Primary squamous cell carcinoma of the thyroid with complete response to radical radiotherapy and concurrent cisplatin-based chemotherapy","volume":"2017","author":"Del Rosario","year":"2017","journal-title":"BMJ Case Rep"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-019-05098-5","article-title":"Prognostic characteristics of primary squamous cell carcinoma of the thyroid: A national cancer database analysis","volume":"44","author":"Limberg","year":"2020","journal-title":"World J Surg"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ12-0174","article-title":"Clinical trial of weekly paclitaxel chemotherapy for papillary thyroid carcinoma with squamous cell carcinoma component","volume":"59","author":"Ito","year":"2012","journal-title":"Endocr J"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.anl.2015.10.011","article-title":"Mixed primary squamous cell carcinoma, follicular carcinoma, and micropapillary carcinoma of the thyroid gland: A case report","volume":"43","author":"Dong","year":"2016","journal-title":"Auris Nasus Larynx"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0373","article-title":"Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers","volume":"24","author":"Pozdeyev","year":"2018","journal-title":"Clin Cancer Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1200\/JCO.2017.73.6785","article-title":"Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600-mutant anaplastic thyroid cancer","volume":"36","author":"Subbiah","year":"2018","journal-title":"J Clin Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0113-0","article-title":"NTRK fusion-positive cancers and TRK inhibitor therapy","volume":"15","author":"Cocco","year":"2018","journal-title":"Nat Rev Clin Oncol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"PO.18.00386","DOI":"10.1200\/po.18.00386","article-title":"et al.Immunophenotype and response to immunotherapy of RET-rearranged lung cancers","volume":"3","author":"Offin","year":"2019","journal-title":"JCO Precis Oncol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0202","article-title":"Remarkable response to ceritinib and brigatinib in an anaplastic lymphoma kinase-rearranged anaplastic thyroid carcinoma previously treated with crizotinib","volume":"30","author":"Leroy","year":"2020","journal-title":"Thyroid"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-021-00326-1","article-title":"Selective multi-kinase inhibition sensitizes mesenchymal pancreatic cancer to immune checkpoint blockade by remodeling the tumor microenvironment","volume":"3","author":"Falcomat\u00e0","year":"2022","journal-title":"Nat Cancer"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-021-00237-1","article-title":"Autophagy inhibition by targeting PIKfyve potentiates response to immune checkpoint blockade in prostate cancer","volume":"2","author":"Qiao","year":"2021","journal-title":"Nat Cancer"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2017.00025","article-title":"Lenvatinib for anaplastic thyroid cancer","volume":"7","author":"Tahara","year":"2017","journal-title":"Front Oncol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/s13045-018-0664-7","article-title":"Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development","volume":"11","author":"Shen","year":"2018","journal-title":"J Hematol Oncol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-17-0558","article-title":"Antitumor effects of anlotinib in thyroid cancer","volume":"26","author":"Ruan","year":"2019","journal-title":"Endocr Relat Cancer"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1610008","DOI":"10.3389\/pore.2021.1610008","article-title":"Using patient-derived xenografts to explore the efficacy of treating head-and-neck squamous cell carcinoma with anlotinib","volume":"27","author":"Hu","year":"2021","journal-title":"Pathol Oncol Res"},{"key":"B41","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1158\/1078-0432.CCR-21-2241","article-title":"Anlotinib induces a T cell-inflamed tumor microenvironment by facilitating vessel normalization and enhances the efficacy of PD-1 checkpoint blockade in neuroblastoma","volume":"28","author":"Su","year":"2022","journal-title":"Clin Cancer Res"},{"key":"B42","doi-asserted-by":"publisher","first-page":"k3529","DOI":"10.1136\/bmj.k3529","article-title":"Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis","volume":"362","author":"Shen","year":"2018","journal-title":"BMJ"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31046-2","article-title":"Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1\/2 dose escalation and expansion trial","volume":"389","author":"El-Khoueiry","year":"2017","journal-title":"Lancet"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.5441","article-title":"Efficacy and safety of pembrolizumab for heavily pretreated patients with advanced, metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: the phase 2 KEYNOTE-180 study","volume":"5","author":"Shah","year":"2019","journal-title":"JAMA Oncol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/nature13954","article-title":"PD-1 blockade induces responses by inhibiting adaptive immune resistance","volume":"515","author":"Tumeh","year":"2014","journal-title":"Nature"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-0386","article-title":"Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers","volume":"16","author":"Goodman","year":"2017","journal-title":"Mol Cancer Ther"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0126-x","article-title":"Immunotherapy in colorectal cancer: rationale, challenges and potential","volume":"16","author":"Ganesh","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.08.019","article-title":"Fusobacterium nucleatum facilitates anti-PD-1 therapy in microsatellite stable colorectal cancer","volume":"42","author":"Wang","year":"2024","journal-title":"Cancer Cell"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.0262","article-title":"Tislelizumab-A promising new option for enhancing chemotherapy benefit in treatment for advanced squamous cell lung cancer","volume":"7","author":"Osarogiagbon","year":"2021","journal-title":"JAMA Oncol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.08.004","article-title":"Fc\u03b3Rs modulate the anti-tumor activity of antibodies targeting the PD-1\/PD-L1 axis","volume":"28","author":"Dahan","year":"2015","journal-title":"Cancer Cell"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-018-2160-x","article-title":"The binding of an anti-PD-1 antibody to Fc\u03b3RI has a profound impact on its biological functions","volume":"67","author":"Zhang","year":"2018","journal-title":"Cancer Immunol Immunother"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-020-01286-z","article-title":"Tislelizumab: first approval","volume":"80","author":"Lee","year":"2020","journal-title":"Drugs"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2023.0573","article-title":"Checkpoint inhibition in addition to dabrafenib\/trametinib for BRAFV600E-mutated anaplastic thyroid carcinoma","volume":"34","author":"Hamidi","year":"2024","journal-title":"Thyroid"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S472196","article-title":"The efficiency and safety of triple-drug combination of albumin-bound paclitaxel, anlotinib and PD-1\/L1 inhibitors in the 2nd or above line of advanced NSCLC: A retrospective cohort study","volume":"16","author":"Li","year":"2024","journal-title":"Cancer Manag Res"},{"key":"B55","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/s41419-020-2511-3","article-title":"anlotinib alters tumor immune microenvironment by downregulating PD-L1 expression on vascular endothelial cells","volume":"11","author":"Liu","year":"2020","journal-title":"Cell Death Dis"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","article-title":"Oncology meets immunology: the cancer-immunity cycle","volume":"39","author":"Chen","year":"2013","journal-title":"Immunity"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-15-0563","article-title":"Adaptive immune resistance: how cancer protects from immune attack","volume":"5","author":"Ribas","year":"2015","journal-title":"Cancer Discovery"},{"key":"B58","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/978-3-030-35805-1_7","article-title":"Relevance of CTC clusters in breast cancer metastasis","volume":"1220","author":"Pi\u00f1eiro","year":"2020","journal-title":"Adv Exp Med Biol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1477954\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T07:10:09Z","timestamp":1742368209000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1477954\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,19]]},"references-count":58,"alternative-id":["10.3389\/fonc.2025.1477954"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1477954","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,19]]},"article-number":"1477954"}}