{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T06:24:23Z","timestamp":1786947863210,"version":"build-2736575974"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"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>Introduction<\/jats:title>\n                    <jats:p>SMARCA4\u2011deficient non\u2011small\u2011cell lung cancer (SMARCA4\u2011dNSCLC) is a rare, aggressive NSCLC subtype driven by SWI\/SNF complex dysfunction with no standardized therapeutic strategies. Although chemoimmunotherapy represents standard first\u2011line therapy for driver\u2011negative advanced NSCLC, its real\u2011world efficacy in SMARCA4\u2011dNSCLC remains controversial. SMARCA4 loss frequently generates an immune\u2011desert tumor microenvironment with low PD\u2011L1 and sparse CD8\u207a T\u2011cell infiltration, potentially conferring intrinsic resistance to immune checkpoint inhibitors (ICIs). Pre\u2011clinical data suggest synergism between anti\u2011angiogenic agents and chemoimmunotherapy; however, real\u2011world evidence comparing chemoimmunotherapy alone versus chemoimmunotherapy plus anti\u2011angiogenics for SMARCA4\u2011dNSCLC is limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single\u2011center retrospective cohort enrolled 22 patients with immunohistochemically\u2011confirmed advanced SMARCA4\u2011dNSCLC treated from January 2021 to September 2024. Clinicopathological characteristics, treatment regimens, survival outcomes and safety data were collected. The Kaplan\u2011Meier method was applied to estimate progression\u2011free survival (PFS) and overall survival (OS). Given the small sample size, only univariate survival analysis was performed. Objective response rate (ORR) and disease control rate (DCR) were evaluated per RECIST 1.1, and treatment\u2011related adverse events were graded using CTCAE v4.0. This study obtained local ethics\u2011committee approval with informed consent waived. The last follow\u2011up date was September 1, 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Most patients were elderly male smokers with high Ki\u201167, frequent adrenal metastasis and low\u2011to\u2011negative PD\u2011L1 expression. Compared with non\u2011ICI\u2011based therapy, ICI\u2011containing regimens achieved significantly superior survival: median OS not reached versus 8.7 months (HR = 0.28, 95%CI:0.08\u20110.98, P = 0.047), accompanied by improved PFS, ORR and DCR. Addition of anti\u2011angiogenic agents brought no extra survival benefit. Elevated CYFRA21\u20111 and poor ECOG\u2011PS predicted unfavorable prognosis. Treatment\u2011related adverse events were generally tolerable across groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Despite an immune\u2011suppressed tumor microenvironment, real\u2011world ICI\u2011containing chemoimmunotherapy delivers meaningful survival benefits for advanced SMARCA4\u2011dNSCLC, whereas additional anti\u2011angiogenic combination yields no further clinical advantage. Our findings should be interpreted cautiously given retrospective design and small sample size. Large\u2011scale multi\u2011center prospective studies incorporating multivariable prognostic analyses are required to validate these results and optimize individualized treatment for this rare molecular NSCLC subtype.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1914598","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:26:32Z","timestamp":1786944392000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunotherapy plus chemotherapy improves survival in SMARCA4-deficient NSCLC: a real-world cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"YuJun","family":"He","sequence":"first","affiliation":[{"name":"Department of Pulmonary Oncology, Cancer Hospital, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YongCun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Oncology, Cancer Hospital, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GuoWei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Oncology, Cancer Hospital, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ShiLiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Oncology, Cancer Hospital, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhiBin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Oncology, Cancer Hospital, Affiliated Hospital of Guangdong Medical University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-0357-3","article-title":"The SWI\/SNF complex in cancer \u2014 biology, biomarkers and therapy","volume":"17","author":"Mittal","year":"2020","journal-title":"Nat Rev Clin Oncol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"28605","DOI":"10.1038\/s41598-025-13913-4","article-title":"The role of SMARCA4 in lung cancer","volume":"15","author":"Wang","year":"2025","journal-title":"Sci Rep"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-21-0433","article-title":"SMARCA4: Implications of an altered chromatin-remodeling gene for cancer development and therapy","volume":"20","author":"Mardinian","year":"2021","journal-title":"Mol Cancer Ther"},{"key":"B4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.lungcan.2022.05.001","article-title":"SMARCA4-deficient lung carcinoma is an aggressive tumor highly infiltrated by FOXP3+ cells and neutrophils","volume":"169","author":"Velut","year":"2022","journal-title":"Lung Cancer"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-1825","article-title":"The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer","volume":"26","author":"Schoenfeld","year":"2020","journal-title":"Clin Cancer Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.6083","article-title":"Clinical characteristics and prognostic analysis of SMARCA4-deficient non-small cell lung cancer","volume":"12","author":"Liang","year":"2023","journal-title":"Cancer Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2019-0633-OA","article-title":"SMARCA4\/BRG1-deficient non-small cell lung carcinomas: A case series and review of the literature","volume":"145","author":"Nambirajan","year":"2021","journal-title":"Arch Pathol Lab Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2020.01.002","article-title":"Clinicopathologic characteristics of BRG1-deficient NSCLC","volume":"15","author":"Dagogo-Jack","year":"2020","journal-title":"J Thorac Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.03.024","article-title":"SMARCA4 and other SWItch\/Sucrose NonFermentable family genomic alterations in NSCLC: Clinicopathologic characteristics and outcomes to immune checkpoint inhibition","volume":"16","author":"Alessi","year":"2021","journal-title":"J Thorac Oncol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1016\/j.ccell.2023.03.018","article-title":"Genomic mapping of metastatic organotropism in lung adenocarcinoma","volume":"41","author":"Lengel","year":"2023","journal-title":"Cancer Cell"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.26349","article-title":"Targeted next-generation sequencing reveals recurrence-associated genomic alterations in early-stage non-small cell lung cancer","volume":"9","author":"Cho","year":"2018","journal-title":"Oncotarget"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113295","article-title":"KEAP1 mutation in lung adenocarcinoma promotes immune evasion and immunotherapy resistance","volume":"42","author":"Zavitsanou","year":"2023","journal-title":"Cell Rep"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1468","article-title":"SMARCA4\/BRG1 is a novel prognostic biomarker predictive of cisplatin-based chemotherapy outcomes in resected non-small cell lung cancer","volume":"22","author":"Bell","year":"2016","journal-title":"Clin Cancer Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.06.019","article-title":"Updated overall survival analysis from IMpower110: Atezolizumab versus platinum-based chemotherapy in treatment-naive programmed death-ligand 1-selected NSCLC","volume":"16","author":"Jassem","year":"2021","journal-title":"J Thorac Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01989","article-title":"Pembrolizumab plus pemetrexed and platinum in nonsquamous non-small-cell lung cancer: 5-year outcomes from the phase 3 KEYNOTE-189 study","volume":"41","author":"Garassino","year":"2023","journal-title":"J Clin Oncol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1200\/JCO.22.01990","article-title":"Pembrolizumab plus chemotherapy in squamous non-small-cell lung cancer: 5-year update of the phase III KEYNOTE-407 study","volume":"41","author":"Novello","year":"2023","journal-title":"J Clin Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyac040","article-title":"Immune-desert tumor microenvironment in thoracic SMARCA4-deficient undifferentiated tumors with limited efficacy of immune checkpoint inhibitors","volume":"27","author":"Gantzer","year":"2022","journal-title":"Oncologist"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.02.017","article-title":"Clinicopathological and genomic correlates of programmed cell death ligand 1 (PD-L1) expression in nonsquamous non-small-cell lung cancer","volume":"31","author":"Lamberti","year":"2020","journal-title":"Ann Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2024.2340154","article-title":"Redoxhigh phenotype mediated by KEAP1\/STK11\/SMARCA4\/NRF2 mutations diminishes tissue-resident memory CD8+ T cells and attenuates the efficacy of immunotherapy in lung adenocarcinoma","volume":"13","author":"Wei","year":"2024","journal-title":"Oncoimmunology"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2023.01.091","article-title":"Clinicopathologic and genomic factors impacting efficacy of first-line chemoimmunotherapy in advanced NSCLC","volume":"18","author":"Alessi","year":"2023","journal-title":"J Thorac Oncol Off Publ Int Assoc For Study Lung Cancer"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2024.108022","article-title":"Effective treatment strategies and key factors influencing therapeutic efficacy in advanced SMARCA4-deficient non-small cell lung cancer","volume":"198","author":"Liu","year":"2024","journal-title":"Lung Cancer (Amsterdam Netherlands)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2024.103472","article-title":"SWI\/SNF family mutations in advanced NSCLC: Genetic characteristics and immune checkpoint inhibitors\u2019 therapeutic implication","volume":"9","author":"Pang","year":"2024","journal-title":"ESMO Open"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3779\/j.issn.1009-3419.2023.101.26","article-title":"Evaluation of efficacy and prognosis analysis of stage III-IV SMARCA4-deficient non-small cell lung cancer treated by PD-1 immune checkpoint inhibitors plus chemotherapy and chemotherapy","volume":"26","author":"Wang","year":"2023","journal-title":"Zhongguo Fei Ai Za Zhi"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.145","article-title":"Improving immune-vascular crosstalk for cancer immunotherapy","volume":"18","author":"Huang","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1265865","article-title":"Research advances in mechanism of antiangiogenic therapy combined with immune checkpoint inhibitors for treatment of non-small cell lung cancer","volume":"14","author":"He","year":"2023","journal-title":"Front Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.lungcan.2019.10.009","article-title":"Non-small cell lung cancer with loss of expression of the SWI\/SNF complex is associated with aggressive clinicopathological features, PD-L1-positive status, and high tumor mutation burden","volume":"138","author":"Naito","year":"2019","journal-title":"Lung Cancer"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-023-00442-4","article-title":"Relationship among DDR gene mutations, TMB and PD-L1 in solid tumour genomes identified using clinically actionable biomarker assays","volume":"7","author":"Wang","year":"2023","journal-title":"NPJ Precis Oncol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41698-024-00797-2","article-title":"Longitudinal genomic profiling using liquid biopsies in metastatic nonsquamous NSCLC following first line immunotherapy","volume":"9","author":"Ding","year":"2025","journal-title":"NPJ Precis Oncol"},{"key":"B29","unstructured":"Non-Small Cell Lung Cancer\n          \n          \n          \n          2026"},{"key":"B30","doi-asserted-by":"publisher","first-page":"288","DOI":"10.21037\/tlcr.2016.06.07","article-title":"Non-small cell lung cancer: Current treatment and future advances","volume":"5","author":"Zappa","year":"2016","journal-title":"Transl Lung Cancer Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2012.06.011","article-title":"Downregulation of SWI\/SNF chromatin remodeling factor subunits modulates cisplatin cytotoxicity","volume":"318","author":"Kothandapani","year":"2012","journal-title":"Exp Cell Res"},{"key":"B32","doi-asserted-by":"publisher","first-page":"5404","DOI":"10.1038\/s41467-021-25260-9","article-title":"SMARCA4\/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca2+ flux to mitochondria","volume":"12","author":"Xue","year":"2021","journal-title":"Nat Commun"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.7150\/thno.69424","article-title":"Platinum-based drugs for cancer therapy and anti-tumor strategies","volume":"12","author":"Zhang","year":"2022","journal-title":"Theranostics"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2024.100773","article-title":"The pharmacogenomic landscape in the Chinese: An analytics of pharmacogenetic variants in 206,640 individuals","volume":"6","author":"Wang","year":"2025","journal-title":"Innovation (Camb)"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N Engl J Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32409-7","article-title":"Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): A randomised, open-label, controlled, phase 3 trial","volume":"393","author":"Mok","year":"2019","journal-title":"Lancet"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1521828","article-title":"SMARCA4-deficient NSCLC treated with first-line tislelizumab and fruquintinib achieved remarkable tumor regression: Case report and literature review","volume":"16","author":"Dong","year":"2025","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.37656","article-title":"Two cases of SMARCA4-deficient non-small cell lung cancer (NSCLC) with improved performance status (PS) after treatment with immune checkpoint inhibitors (ICIs)","volume":"15","author":"Koizumi","year":"2023","journal-title":"Cureus"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13122048","article-title":"Dynamic and static 18F-FDG PET\/CT imaging in SMARCA4-deficient non-small cell lung cancer and response to therapy: A case report","volume":"13","author":"Wumener","year":"2023","journal-title":"Diagnostics (Basel)"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2020.11.025","article-title":"Atezolizumab plus chemotherapy for first-line treatment of nonsquamous NSCLC: Results from the randomized phase 3 IMpower132 trial","volume":"16","author":"Nishio","year":"2021","journal-title":"J Thorac Oncol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2020.5601","article-title":"A genomic-pathologic annotated risk model to predict recurrence in early-stage lung adenocarcinoma","volume":"156","author":"Jones","year":"2021","journal-title":"JAMA Surg"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.21037\/qims-23-1813","article-title":"SMARCA4-deficient non-small cell lung cancer: A case description and literature analysis","volume":"14","author":"Ye","year":"2024","journal-title":"Quant Imaging Med Surg"},{"key":"B43","doi-asserted-by":"publisher","first-page":"103506","DOI":"10.1016\/j.jtho.2025.10.013","article-title":"Neoadjuvant immunochemotherapy in resectable NSCLC with SMARCA4 alterations","volume":"21","author":"Peng","year":"2025","journal-title":"J Thorac Oncol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-012288","article-title":"Genetic drivers of tumor microenvironment and immunotherapy resistance in non-small cell lung cancer: The role of KEAP1, SMARCA4, and PTEN mutations","volume":"13","author":"Paredes","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B45","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41698-025-00838-4","article-title":"A phase II trial of mTORC1\/2 inhibition in STK11 deficient non small cell lung cancer","volume":"9","author":"Middleton","year":"2025","journal-title":"NPJ Precis Oncol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1453895","article-title":"Long-term follow-up of combination therapy with pembrolizumab and anlotinib in thoracic SMARCA4-deficient undifferentiated tumor: A case report and molecular features","volume":"14","author":"Duan","year":"2024","journal-title":"Front Oncol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.217282","article-title":"SMARCA4 and SMARCA2 co-deficiency: An uncommon molecular signature defining a subset of rare, aggressive and undifferentiated Malignancies associated with defective chromatin remodeling","volume":"605","author":"Field","year":"2024","journal-title":"Cancer Lett"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-1744","article-title":"BRG1 loss predisposes lung cancers to replicative stress and ATR dependency","volume":"80","author":"Gupta","year":"2020","journal-title":"Cancer Res"},{"key":"B49","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/s41467-019-08380-1","article-title":"SMARCA4 loss is synthetic lethal with CDK4\/6 inhibition in non-small cell lung cancer","volume":"10","author":"Xue","year":"2019","journal-title":"Nat Commun"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1914598\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:26:34Z","timestamp":1786944394000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1914598\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":49,"alternative-id":["10.3389\/fimmu.2026.1914598"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1914598","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]},"article-number":"1914598"}}