Context-Dependent Survival Associations Between Interleukin-13 Expression and Immunotherapy in Advanced Solid Tumors

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Interleukin-13 (IL-13) plays a role in tumor immunosurveillance, but its impact on immunotherapy outcomes is not fully understood.
• Understanding the relationship between IL-13 and treatment response is crucial for advancing cancer immunotherapy.

Purpose of the Study:

• To investigate the association between IL-13 expression levels and outcomes in patients with advanced or metastatic cancers.
• To explore the correlation of IL-13 with other immune biomarkers and its interaction with immunotherapy treatments.

Main Methods:

• Tumor RNA sequencing was performed on 514 advanced/metastatic cancer samples to quantify IL-13 expression.
• IL-13 expression was categorized as high (75th-100th percentile) or non-high (0-74th percentile) and correlated with clinical data and other immune markers.
• Survival analyses were conducted for immunotherapy-naïve patients and interaction analyses were performed between IL-13 levels and immunotherapy treatment.

Main Results:

• High IL-13 expression was observed in 16.1% of patients, most frequently in sarcomas, and correlated with IL-4, IL-2Rα, TIM3, PD-L1 negativity, and microsatellite instability.
• In immunotherapy-naïve patients, high IL-13 was associated with significantly shorter overall survival (OS) compared to non-high IL-13.
• Immunotherapy treatment was linked to decreased OS in patients with non-high IL-13, whereas no significant difference was observed in patients with high IL-13.

Conclusions:

• High IL-13 RNA levels are linked to distinct immunoregulatory biomarkers and are prevalent in sarcomas.
• Elevated IL-13 expression predicts poor OS in immunotherapy-naïve patients.
• The findings suggest IL-13 may serve as a predictive biomarker for immunotherapy response and warrants further validation for patient stratification.