ArticleImmunoTargets and therapy2026
Context-Dependent Survival Associations Between Interleukin-13 Expression and Immunotherapy in Advanced Solid Tumors.
Article in ImmunoTargets and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Interleukin (IL)-13 can modulate tumor immunosurveillance. The interplay between IL-13 and immunotherapy outcomes has not been well elucidated. Methods: IL-13 expression was evaluated by tumor RNA sequencing (514 tumors; advanced/metastatic cancers). Transcripts were normalized to internal housekeeping genes and standardized relative to a reference population (735 tumors; 35 histologies) and ranked as percentile values: IL-13-high (75th-100th percentile) and non-high (0-74th percentile). Results: Overall, 39.7% of 514 patients were men; median age, 61 years; 489 had clinical data annotation (217 immunotherapy treated; 272, immunotherapy naïve). Eighty-three of 514 patients (16.1%) showed high IL-13 expression, which was most common in sarcomas (29.2%) and independently correlated with high expression of IL-4 (odds ratio (OR)=4.20) and IL-2Rα (OR=4.63), non-high expression of TIM3 (OR=0.40), PD-L1 negativity (OR=0.40), and microsatellite instability (OR=4.03). In the immunotherapy-naïve analysis, patients with high versus non-high IL-13 levels had shorter overall survival (OS) from metastatic/advanced disease diagnosis (median, 24.5 versus 43.3 months) (HR 1.70, 95% CI 1.15-2.52, log-rank p=0.007). Interaction analysis between IL-13 levels and immunotherapy demonstrated that, among patients with non-high IL-13, those treated with immunotherapy had significantly shorter OS versus immunotherapy-naïve patients (p<0.001), whereas patients with high IL-13 levels had no significant difference in OS between immunotherapy treatment and naive groups. Conclusion: High IL-13 RNA levels were associated with other important immunoregulatory biomarkers and were most common in sarcomas. High IL-13 expression correlated with poor OS in immunotherapy-naïve patients. The observation that immunotherapy was associated with decreased survival among patients with non-high IL-13 levels is intriguing. These findings are hypothesis-generating, require validation, and have potential implications for biomarker-driven patient stratification to enhance their translational relevance.
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