ArticleCancer research communications2025
The Impact of the Tumor Microenvironment on the Effect of IL-1β Blockade in NSCLC: Biomarker Analyses from CANOPY-1 and CANOPY-N Trials.
Article in Cancer research communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Canakinumab with chemoradiation and durvalumab consolidation in unresectable stage III non-small cell lung cancer: the phase I/II CHORUS trial.Nature communications · 2026Trial
- The double face of IL-1β in lung cancer.Oncoimmunology · 2026Article
- Targeting CRTC2 reversesProceedings of the National Academy of Sciences of the United States of America · 2026Article
- IL-1β-mediated suppression of CIITA attenuates IFN-γ-induced MHC-II expression on Fibroblasts.Cell communication and signaling : CCS · 2025Article
- Defining Non-small Cell Lung Cancer Tumor Microenvironment Changes at Primary and Acquired Immune Checkpoint Inhibitor Resistance Using Clinical and Real-World Data.Cancer research communications · 2025Article
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Authors and funding
19 authors.
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Abstract
abstractPreclinical studies have shown that interleukin (IL)-1β blockade can modulate the tumor microenvironment (TME) to activate antitumor immunity and, in combination with immune checkpoint inhibitors (ICIs), prevent cancer growth. Our study investigates if immune biomarkers in the TME affect outcomes in patients with non–small cell lung cancer (NSCLC) treated with the IL-1β inhibitor canakinumab plus an ICI-based therapy and describes canakinumab effects on the TMEs in these patients. Exploratory analyses were conducted in two prospective trials evaluating canakinumab combined with pembrolizumab-based regimens in patients with NSCLC: CANOPY-1 (first-line setting) and CANOPY-N (neoadjuvant setting). Immunohistochemistry (IHC) and transcriptomic analyses were performed on baseline tumor samples from CANOPY-1, and IHC and multiplex immunofluorescence analyses were performed on baseline and posttreatment tumor samples from CANOPY-N. Associations with clinical outcomes were evaluated. In CANOPY-1, in patients with low levels of T-cell infiltration in the tumor, the addition of canakinumab to a pembrolizumab-based regimen was associated with progression-free and overall survival improvements. Low levels of T-cell infiltration were associated with an immunosuppressive gene expression phenotype, supporting the role of low T-cell infiltration as a surrogate of an overall immunosuppressive TME. In CANOPY-N, a reduction in immunosuppressive cells in the TME was observed following canakinumab and pembrolizumab treatment. Our exploratory biomarker analyses from the CANOPY-1 and CANOPY-N trials suggest that IL-1β blockade may shift the TME toward an immune-activated status and that patients with immunosuppressive TME features could benefit from the addition of canakinumab to an ICI-based treatment. SIGNIFICANCE: Patients with NSCLC with immunosuppressive tumor features and low T-cell infiltration derive less benefit from ICI-based treatment. Biomarker analyses presented here suggest that these patients may benefit from the addition of anti-IL-1β therapy to their treatment.
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