The promise of IL-1β modulation in NSCLC clinical context

Emerging preclinical evidence challenges the long-standing assumption that Interleukin-1β (IL-1β) uniformly promotes non-small cell lung cancer (NSCLC). We show that, in the context of chemo-immunotherapy, IL-1β enhances anti-tumor immunity by inducing tumor-cell CXCL10 expression and recruiting CD8<sup>+</sup> T cells, thereby sensitizing "cold" tumors to treatment. These findings contrast sharply with the failure of multiple CANOPY trials targeting IL-1β, suggesting that blockade may be effective only in prevention or early carcinogenesis. Instead, controlled IL-1β activation, guided by biomarkers and combined with chemotherapy plus PD-1 blockade, may represent a promising strategy to overcome resistance in established NSCLC.

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Publication Details

Journal
Frontiers in Immunology
Published
2026-01-30
DOI
https://doi.org/10.3389/fimmu.2026.1773253
Primary Topic
Chemokine receptors and signaling
Type
article
Field-Weighted Citation Impact
0.00

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article

The promise of IL-1β modulation in NSCLC clinical context

Cédric Rébé, François Ghiringhelli
Frontiers in Immunology
Chemokine receptors and signaling
article

The promise of IL-1β modulation in NSCLC clinical context

Cédric Rébé, François Ghiringhelli
article en

Abstract

Emerging preclinical evidence challenges the long-standing assumption that Interleukin-1β (IL-1β) uniformly promotes non-small cell lung cancer (NSCLC). We show that, in the context of chemo-immunotherapy, IL-1β enhances anti-tumor immunity by inducing tumor-cell CXCL10 expression and recruiting CD8<sup>+</sup> T cells, thereby sensitizing "cold" tumors to treatment. These findings contrast sharply with the failure of multiple CANOPY trials targeting IL-1β, suggesting that blockade may be effective only in prevention or early carcinogenesis. Instead, controlled IL-1β activation, guided by biomarkers and combined with chemotherapy plus PD-1 blockade, may represent a promising strategy to overcome resistance in established NSCLC.

Frontiers in ImmunologyVol. 17
Inserm (FR), Centre Georges François Leclerc (FR)
Ligue Contre le Cancer, Institut National Du Cancer
Good health and well-being
Openalex Percentile: Top 73%
Chemokine receptors and signaling
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