{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:20:46Z","timestamp":1780633246576,"version":"3.54.1"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"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>Anaplastic thyroid carcinoma (ATC) is a rare and highly aggressive malignancy characterized by a poor prognosis, with a median survival time of approximately 3 to 4 months. In this report, we present a case involving a 59-year-old patient diagnosed with ATC, who experienced swift local recurrence and pulmonary metastasis following radical thyroidectomy. Comprehensive Sanger sequencing of the resected tumor tissue revealed no mutations in the TERT promoter or the BRAF V600E gene. The patient exhibited rapid recurrence post-surgery and was deemed unsuitable for immediate surgical intervention. The patient was unable to tolerate chemotherapy; therefore, radiotherapy was administered initially to prevent airway compression resulting from disease progression. During the course of radiotherapy, pulmonary metastasis developed, yet the patient remained intolerant to both chemotherapy and anti-angiogenic therapy. Immunohistochemical analysis revealed a high expression of PD-L1. Whole exome sequencing (WES) indicated a tumor mutation burden (TMB) of 2.98 mut\/Mb, microsatellite stability (MSS), and identified 10 missense mutations, 1 nonsense mutation, and 1 frameshift insertion. However, none of these mutations have corresponding targeted therapies. Consequently, we administered tislelizumab as an immunotherapeutic intervention. The patient exhibited significant regression in cervical metastatic lymph nodes and pulmonary metastatic tumors, achieving a sustained remission lasting 14 months, culminating in complete remission, without experiencing any adverse events related to immune checkpoint inhibitors. This case demonstrates the efficacy of second-line monotherapy with an immune checkpoint inhibitor (ICI) for ATC in a patient unable to tolerate chemotherapy and anti-angiogenic anlotinib treatment, thereby offering a viable treatment strategy for ATC patients.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1544604","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T07:27:07Z","timestamp":1739345227000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A remarkable and durable response to tislelizumab treatment of an anaplastic thyroid carcinoma without targetable genomic alterations: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Jingjing","family":"Chai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuwen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senyuan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguo","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.21037\/gs.2019.10.18","article-title":"Novel treatments for anaplastic thyroid carcinoma","volume":"9","author":"Ferrari","year":"2020","journal-title":"Gland Surg"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2019-00007","article-title":"Targeted therapy for advanced thyroid cancer: kinase inhibitors and beyond","volume":"40","author":"Cabanillas","year":"2019","journal-title":"Endocr Rev"},{"key":"B3","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 Off J Am Thyroid Assoc"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1099280","article-title":"Molecular features of aggressive thyroid cancer","volume":"12","author":"Elia","year":"2022","journal-title":"Front Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-023-03390-y","article-title":"Efficacy and safety of anlotinib-based chemotherapy for locally advanced or metastatic anaplastic thyroid carcinoma","volume":"81","author":"Zheng","year":"2023","journal-title":"Endocrine"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002284","article-title":"PD-L1 expression and its modulating factors in anaplastic thyroid carcinoma: A multi-institutional study","volume":"48","author":"Agarwal","year":"2024","journal-title":"Am J Surg Pathol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1672","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":"B8","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":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0561-4","article-title":"Immunological impact of cell death signaling driven by radiation on the tumor microenvironment","volume":"21","author":"Rodriguez-Ruiz","year":"2020","journal-title":"Nat Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.canlet.2020.12.045","article-title":"Radiotherapy, immunotherapy, and the tumour microenvironment: Turning an immunosuppressive milieu into a therapeutic opportunity","volume":"502","author":"Donlon","year":"2021","journal-title":"Cancer Lett"},{"key":"B11","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":"B12","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1089\/thy.2019.0650","article-title":"Molecular determinants of thyroid nodules with indeterminate cytology and RAS mutations","volume":"31","author":"Hernandez-Prera","year":"2021","journal-title":"Thyroid"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2016.02.008","article-title":"Immunohistochemical detection of NRAS(Q61R) protein in follicular-patterned thyroid tumors","volume":"53","author":"Oishi","year":"2016","journal-title":"Hum Pathol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1038\/s41392-023-01705-z","article-title":"Targeting the RAS\/RAF\/MAPK pathway for cancer therapy: from mechanism to clinical studies","volume":"8","author":"Bahar","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B15","doi-asserted-by":"publisher","first-page":"266","DOI":"10.3390\/cancers11020266","article-title":"Identification of novel HLA class II-restricted neoantigens derived from driver mutations","volume":"11","author":"Iiizumi","year":"2019","journal-title":"Cancers"},{"key":"B16","doi-asserted-by":"publisher","first-page":"100002","DOI":"10.1016\/j.esmoop.2020.100002","article-title":"Molecular profiling of Asian patients with advanced melanoma receiving check-point inhibitor treatment","volume":"6","author":"Byeon","year":"2021","journal-title":"ESMO Open"},{"key":"B17","doi-asserted-by":"publisher","first-page":"475","DOI":"10.3390\/cancers13030475","article-title":"No impact of NRAS mutation on features of primary and metastatic melanoma or on outcomes of checkpoint inhibitor immunotherapy: an Italian melanoma intergroup (IMI) study","volume":"13","author":"Guida","year":"2021","journal-title":"Cancers"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1090737","article-title":"Objective response to immune checkpoint inhibitor therapy in NRAS-mutant melanoma: A systematic review and meta-analysis","volume":"10","author":"Jaeger","year":"2023","journal-title":"Front Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/s41419-024-06469-0","article-title":"FSTL3 promotes tumor immune evasion and attenuates response to anti-PD1 therapy by stabilizing c-Myc in colorectal cancer","volume":"15","author":"Li","year":"2024","journal-title":"Cell Death Dis"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.717505","article-title":"Follistatin-like 3 correlates with lymph node metastasis and serves as a biomarker of extracellular matrix remodeling in colorectal cancer","volume":"12","author":"Yang","year":"2021","journal-title":"Front Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"102806","DOI":"10.1016\/j.eclinm.2024.102806","article-title":"Long-term survival and post-hoc analysis of toripalimab plus definitive chemoradiotherapy for oesophageal squamous cell carcinoma: insights from the EC-CRT-001 phase II trial","volume":"75","author":"Wang","year":"2024","journal-title":"EClinicalMedicine"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1544604\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T07:27:09Z","timestamp":1739345229000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1544604\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,12]]},"references-count":21,"alternative-id":["10.3389\/fimmu.2025.1544604"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1544604","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,12]]},"article-number":"1544604"}}