{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:48:14Z","timestamp":1792532894932,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"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>\n                    Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) are rare malignancies characterized by resistance to chemotherapy and poor clinical outcomes. While immunotherapy have shown promise, especially in the first-line treatment, effective therapeutic strategies for patients with PD-L1-negative tumors and complex genomic profiles remain undefined. We report a case of chemorefractory SMARCA4-UT in a patient presenting with cervical mass. CGP revealed pathogenic\n                    <jats:italic>SMARCA4<\/jats:italic>\n                    ,\n                    <jats:italic>TP53<\/jats:italic>\n                    , and\n                    <jats:italic>CDKN2A<\/jats:italic>\n                    mutations. Despite PD-L1 negativity, the tumor exhibited TMB-H and a dominant smoking signature. Guided by precision oncology targeting both immunogenic profile and cell-cycle dysregulation, the patient was treated with dual immunotherapy (pembrolizumab plus ipilimumab) combined with the CDK4\/6 inhibitor palbociclib. This novel regimen elicited a metabolic partial response within 1.5 months, which has been sustained for over 4 months. To our knowledge, this is the first report demonstrating the efficacy of dual checkpoint blockade plus CDK4\/6 inhibition in SMARCA4-UT. This case highlights potential of biomarker-driven therapies to overcome resistance in rare thoracic neoplasms.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1858358","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:39:04Z","timestamp":1779169144000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["CDK4\/6 inhibition with dual immunotherapy in chemorefractory SMARCA4-deficient undifferentiated tumor: a case report"],"prefix":"10.3389","volume":"17","author":[{"given":"\u00dcnal Metin","family":"Tokat","sequence":"first","affiliation":[{"name":"Precision Oncology Center, Medicana Health Group","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eevval Nur","family":"Bilgi\u00e7","sequence":"additional","affiliation":[{"name":"Precision Oncology Center, Medicana Health Group","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashkan","family":"Adibi","sequence":"additional","affiliation":[{"name":"Precision Oncology Center, Medicana Health Group","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esranur","family":"Ayd\u0131n","sequence":"additional","affiliation":[{"name":"Precision Oncology Center, Medicana Health Group","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onur","family":"Tutar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cerrahpasa Faculty of Medicine, Istanbul University","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilal","family":"Cans\u0131z","sequence":"additional","affiliation":[{"name":"Ear Nose and Throat Clinic, Istanbul Haseki Training and Research Hospital","place":["Sultangazi, Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Y\u0131lmaz","family":"Altay","sequence":"additional","affiliation":[{"name":"Department of Medical Pathology, Department of Surgical Medical Sciences, Istanbul Faculty of Medicine, Istanbul University","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nalan","family":"Akgul Babacan","sequence":"additional","affiliation":[{"name":"Precision Oncology Center, Medicana Health Group","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyl\u00fcl","family":"\u00d6zg\u00fc","sequence":"additional","affiliation":[{"name":"Precision Oncology Center, Medicana Health Group","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina Melisa","family":"Manea","sequence":"additional","affiliation":[{"name":"Precision Oncology Center, Medicana Health Group","place":["Istanbul, 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