{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T16:02:05Z","timestamp":1773849725582,"version":"3.50.1"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nuclear protein in testis (NUT) carcinoma is an extremely rare and highly aggressive epithelial malignancy driven by NUTM1 rearrangements. Sinonasal involvement is uncommon and often presents with non-specific clinical and radiologic features, leading to delayed diagnosis. Optimal management remains undefined, and outcomes are poor when complete resection is not feasible.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>A 31-year-old man developed progressive numbness and swelling of the left cheek after tooth extraction. Imaging revealed a soft-tissue mass involving the left maxillary sinus with adjacent maxillofacial soft-tissue extension. Endoscopic biopsy demonstrated a poorly differentiated carcinoma with diffuse punctate nuclear NUT expression, high proliferative index (Ki-67 ~50%), and PD-L1 expression in both tumor cells and immune cells. ^18F-FDG PET-CT showed no regional or distant metastases. Given unresectability, the patient received toripalimab (240 mg) combined with docetaxel and cisplatin every 3 weeks. MRI after three cycles showed early radiologic improvement, and further tumor regression was observed after six cycles, consistent with a partial response. The patient subsequently continued on toripalimab-based maintenance therapy with ongoing stable residual disease at the latest follow-up (approximately 5 months after therapy initiation and 6 months from diagnosis).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>To our knowledge, this is the first reported case of toripalimab-based chemoimmunotherapy demonstrating an early partial response and short-term disease control in unresectable maxillary sinus NUT carcinoma. It supports the potential role of PD-1 blockade integrated with platinum\u2013taxane chemotherapy as a component of multimodal management for sinonasal NUT carcinomas.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1763340","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T05:18:50Z","timestamp":1771910330000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Toripalimab-based chemoimmunotherapy for unresectable sinonasal NUT carcinoma of the maxillary sinus: a case report"],"prefix":"10.3389","volume":"17","author":[{"given":"Dan","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]},{"name":"Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]},{"name":"Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinglong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghui","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]},{"name":"Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"B1","article-title":"BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma","volume":"63","author":"French","year":"2003","journal-title":"Cancer Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.860830","article-title":"NUT carcinoma: clinicopathologic features, molecular genetics and epigenetics","volume":"12","author":"Moreno","year":"2022","journal-title":"Front Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-1153","article-title":"Clinicopathologic features and long-term outcomes of NUT midline carcinoma","volume":"18","author":"Bauer","year":"2012","journal-title":"Clin Cancer Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-013-0428-1","article-title":"The importance of diagnosing NUT midline carcinoma","volume":"7","author":"French","year":"2013","journal-title":"Head Neck Pathol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1002\/hed.27553","article-title":"Sinonasal NUT carcinoma: a consecutive case series and systematic review","volume":"46","author":"Ramesh","year":"2024","journal-title":"Head Neck"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2023.1098704","article-title":"Sinonasal NUT carcinoma: a retrospective case series from a single institution","volume":"10","author":"Wang","year":"2023","journal-title":"Front Surg"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-021-01311-x","article-title":"Sinonasal NUT carcinoma: delayed diagnosis due to the COVID-19 pandemic and a review of the literature","volume":"15","author":"Crocetta","year":"2021","journal-title":"Head Neck Pathol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e318198d666","article-title":"Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody","volume":"33","author":"Haack","year":"2009","journal-title":"Am J Surg Pathol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31815a3900","article-title":"NUT rearrangement in undifferentiated carcinomas of the upper aerodigestive tract","volume":"32","author":"Stelow","year":"2008","journal-title":"Am J Surg Pathol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-0591","article-title":"Report of the first international symposium on NUT carcinoma","volume":"28","author":"French","year":"2022","journal-title":"Clin Cancer Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.7741-21","article-title":"Complete response induced by concurrent chemoradiotherapy in a patient with NUT carcinoma","volume":"61","author":"Muramatsu","year":"2022","journal-title":"Intern Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1368187","article-title":"Case report: Consolidation immunotherapy after concurrent chemoradiotherapy in sinonasal NUT carcinoma","volume":"14","author":"Geng","year":"2024","journal-title":"Front Oncol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"67","DOI":"10.36401\/JIPO-23-19","article-title":"Sustained clinical response to immunotherapy followed by BET inhibitor in a patient with unresectable sinonasal NUT carcinoma","volume":"7","author":"Herbison","year":"2024","journal-title":"J Immunother Precis Oncol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4103\/jcrt.jcrt_1083_22","article-title":"Immunotherapy experience in sinonasal NUT midline carcinoma: case report","volume":"20","author":"Caner","year":"2024","journal-title":"J Cancer Res Ther"},{"key":"B15","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1186\/s13023-020-01449-x","article-title":"Clinical features, treatment, and survival outcome of primary pulmonary NUT midline carcinoma","volume":"15","author":"Xie","year":"2020","journal-title":"Orphanet J Rare Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1094770","article-title":"The whole treatment process and thinking of a patient with NUT carcinoma of the parotid gland: a case report","volume":"13","author":"Fu","year":"2023","journal-title":"Front Oncol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/s12967-023-04017-6","article-title":"Immunogenic cell death in cancer: concept and therapeutic implications","volume":"21","author":"Galluzzi","year":"2023","journal-title":"J Transl Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1412070","article-title":"Case report: Long term remission of metastatic sinonasal NUT carcinoma after palliative radiotherapy and immunotherapy in an elderly patient","volume":"14","author":"Ng","year":"2025","journal-title":"Front Oncol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1200\/JCO.21.02508","article-title":"Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: updated results of the phase III KEYNOTE-048 study","volume":"41","author":"Harrington","year":"2023","journal-title":"J Clin Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2020.10.016","article-title":"Prolonged disease control on nivolumab for primary pulmonary NUT carcinoma","volume":"22","author":"Davis","year":"2021","journal-title":"Clin Lung Cancer"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1571776","article-title":"Neoadjuvant toripalimab combined with chemotherapy in locally advanced HNSCC","volume":"15","author":"Wang","year":"2025","journal-title":"Front Oncol"},{"key":"B22","article-title":"Toripalimab plus gemcitabine and cisplatin versus placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (JUPITER-02): a randomised, double-blind, phase 3 trial","volume":"397","author":"Zhang","year":"2021","journal-title":"Lancet"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.20181","article-title":"Toripalimab plus gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma (JUPITER-02)","volume":"330","author":"Mai","year":"2023","journal-title":"JAMA"}],"updated-by":[{"DOI":"10.3389\/fimmu.2026.1828382","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000}}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1763340\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:08:10Z","timestamp":1773828490000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1763340\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,24]]},"references-count":23,"alternative-id":["10.3389\/fimmu.2026.1763340"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1763340","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,24]]},"article-number":"1763340"}}