ArticleCancer discovery2023
Genomic Instability and Protumoral Inflammation Are Associated with Primary Resistance to Anti-PD-1 + Antiangiogenesis in Malignant Pleural Mesothelioma.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02856425 (Phase Ib Trial Of Pembrolizumab And Nintedanib), which is not on this map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Phase Ib Trial Of Pembrolizumab And Nintedanib
Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Constitutive inflammation and epithelial-mesenchymal transition dictate sensitivity to nivolumab in CONFIRM: a placebo-controlled, randomised phase III trial.Nature communications · 2025Trial
- Short Report of a Phase II Trial of Nintedanib in Recurrent Malignant Pleural Mesothelioma (MPM).Clinical lung cancer · 2023Trial
- Loss of tumor suppressor NF2 mediates resistance to CAR T cell and anti-PD-1 therapy: Strategies to restore immunotherapy sensitivity.Med (New York, N.Y.) · 2026Article
- Multiplexed single-cell and spatial profiling reveal B cells and tertiary lymphoid structures as prognostic indicators in pleural mesothelioma.British journal of cancer · 2026Article
- IL‑6: A key player in the EGFR‑TKI‑resistant tumor microenvironment and its therapeutic implications (Review).International journal of oncology · 2026Review
- Multi-omics integration reveals tumor and microenvironmental heterogeneity in malignant pleural mesothelioma.Discover oncology · 2026Article
- Identification of CXCL8 as a potential gene associated with lymph node metastasis in papillary thyroid carcinoma through bioinformatics analysis.Scientific reports · 2025Article
- Development of a Mesothelin-Binding Engineered Scaffold Protein as a Theranostic for Pleural Mesothelioma.Bioconjugate chemistry · 2025Article
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- Interferon Epsilon Loss Is Elusive 9p21 Link to Immune-Cold Tumors, Resistant to Immune Checkpoint Therapy, and Endogenous CXCL9/10 Induction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Review
- Review
- The role of the CXC chemokine family in endometriosis research and its therapeutic potential.Journal of molecular histology · 2025Review
- Clinical Interest in Exome-Based Analysis of Somatic Mutational Signatures for Non-Small Cell Lung Cancer.Cancers · 2024Article
- Inhibition of SUV39H1 reduces tumor angiogenesis via Notch1 in oral squamous cell carcinoma.PeerJ · 2024Article
- Genomic instability as a driver and suppressor of anti-tumor immunity.Frontiers in immunology · 2024Review
- MDSCs-derived GPR84 induces CD8Journal for immunotherapy of cancer · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
43 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer immunotherapy combinations have recently been shown to improve the overall survival of advanced mesotheliomas, especially for patients responding to those treatments. We aimed to characterize the biological correlates of malignant pleural mesotheliomas' primary resistance to immunotherapy and antiangiogenics by testing the combination of pembrolizumab, an anti-PD-1 antibody, and nintedanib, a pan-antiangiogenic tyrosine kinase inhibitor, in the multicenter PEMBIB trial (NCT02856425). Thirty patients with advanced malignant pleural mesothelioma were treated and explored. Unexpectedly, we found that refractory patients were actively recruiting CD3+CD8+ cytotoxic T cells in their tumors through CXCL9 tumor release upon treatment. However, these patients displayed high levels of somatic copy-number alterations in their tumors that correlated with high blood and tumor levels of IL6 and CXCL8. Those proinflammatory cytokines resulted in higher tumor secretion of VEGF and tumor enrichment in regulatory T cells. Advanced mesothelioma should further benefit from stratified combination therapies adapted to their tumor biology. SIGNIFICANCE: Sequential explorations of fresh tumor biopsies demonstrated that mesothelioma resistance to anti-PD-1 + antiangiogenics is not due to a lack of tumor T-cell infiltration but rather due to adaptive immunosuppressive pathways by tumors, involving molecules (e.g., IL6, CXCL8, VEGF, and CTLA4) that are amenable to targeted therapies. This article is highlighted in the In This Issue feature, p. 799.
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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.