ArticleThe oncologist2022
Immune-Desert Tumor Microenvironment in Thoracic SMARCA4-Deficient Undifferentiated Tumors with Limited Efficacy of Immune Checkpoint Inhibitors.
Article in The oncologist, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Associations between tertiary lymphoid structure density and immune checkpoint inhibitor efficacy in solid tumors: systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- Tazemetostat, an EZH2 inhibitor, in solid tumors harboring SWI/SNF alterations: a phase II basket study.Nature communications · 2026Trial
- A thoracic SMARCA4-deficient undifferentiated tumor: A case report.Oncology letters · 2026Article
- Low-dose radiotherapy as an immunomodulator in cancer: dose-specific mechanisms and hybrid high-dose/low-dose strategies.Biomarker research · 2026Review
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Thoracic SMARCA4-Deficient Undifferentiated Tumor Presenting as a Giant Mediastinal Mass: A Case Report.The American journal of case reports · 2026Article
- ThoracicJournal of thoracic disease · 2026Article
- Bibliometric analysis and knowledge mapping of thoracic SMARCA4-deficient undifferentiated tumor.Discover oncology · 2026Article
- [Radiotherapy for SMARCA4-deficient Pulmonary Neoplasms: Efficacy and Related Parameter Analysis].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Article
- SMARCA4-deficient non-small cell lung cancer and immunotherapy resistance: mechanisms and novel strategies-a mini-review.Discover oncology · 2026Review
- CDK4/6 inhibition with dual immunotherapy in chemorefractory SMARCA4-deficient undifferentiated tumor: a case report.Frontiers in immunology · 2026Article
- Immunotherapy plus chemotherapy improves survival in SMARCA4-deficient NSCLC: a real-world cohort study.Frontiers in immunology · 2026Article
- First-Line Treatment of Advanced Thoracic SMARCA4-Deficient Undifferentiated Tumor: A Case Report and Review of the Literature.Case reports in oncological medicine · 2026Article
- Potential efficacy of anti-angiogenic therapy combined with immunotherapy for advanced SMARCA4-deficient thoracic tumor: a retrospective study.Translational lung cancer research · 2025Article
- Transformation of Thoracic SMARCA4-Deficient Undifferentiated Tumour to Squamous Cell Carcinoma: A Case Report.Respirology case reports · 2025Article
- Clinicopathological and molecular characteristics and treatment outcomes of SMARCA4-deficient thoracic tumors: a comprehensive analysis.The oncologist · 2025Article
- Long-term survival of a SMARCA4-deficient undifferentiated thoracic tumor with brain metastasis successfully treated with multimodal treatment: a case report and literature review.Journal of cancer research and clinical oncology · 2025Review
- Genetic drivers of tumor microenvironment and immunotherapy resistance in non-small cell lung cancer: the role ofJournal for immunotherapy of cancer · 2025Review
- Thoracic SMARCA4-deficient undifferentiated tumor: diagnostic characteristics, molecular insights, and treatment approaches.The oncologist · 2025Article
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Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) are aggressive neoplasms. Data linking BAF alterations with tumor microenvironment (TME) and efficacy of immune checkpoint inhibitors (ICI) are contradictory. The TME of SMARCA4-UT and their response to ICI are unknown. MATERIALS AND
methodsPatients diagnosed with SMARCA4-UT in our institution were included. Immunostainings for tertiary lymphoid structures (TLS), immune cell markers, and checkpoints were assessed. Validation was performed using an independent transcriptome dataset including SMARCA4-UT, non-small cell lung cancers (NSCLC) with/without SMARCA4 mutations, and unclassified thoracic sarcomas (UTS). CXCL9 and PD-L1 expressions were assessed in NSCLC and thoracic fibroblast cell lines, with/without SMARCA4 knockdown, treated with/without interferon gamma.
resultsNine patients were identified. All samples but one showed no TLS, consistent with an immune desert TME phenotype. Four patients received ICI as part of their treatment, but the only one who responded, had a tumor with a TLS and immune-rich TME. Unsupervised clustering of the validation cohort using immune cell scores identified 2 clusters associated with cell ontogeny and immunity (cluster 1 enriched for NSCLC independently of SMARCA4 status (n = 9/10; P = .001); cluster 2 enriched for SMARCA4-UT (n = 11/12; P = .005) and UTS (n = 5/5; P = .0005). SMARCA4 loss-of-function experiments revealed interferon-induced upregulation of CXCL9 and PD-L1 expression in the NSCLC cell line with no effect on the thoracic fibroblast cell line.
conclusionSMARCA4-UT mainly have an immune desert TME with limited efficacy to ICI. TME of SMARCA4-driven tumors varies according to the cell of origin questioning the interplay between BAF alterations, cell ontogeny and immunity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.