Prognostic Significance and Emerging Predictive Potential of Interleukin-1β Expression in Oncogene-Driven NSCLC

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genomics

Background:

• Preclinical data suggest interleukin-1β (IL-1β) affects non-small cell lung cancer (NSCLC) tumor behavior.
• Clinical trials investigating IL-1β inhibition in NSCLC have yielded mixed results, highlighting the need to understand its role in specific molecular subtypes.

Purpose of the Study:

• To evaluate the prognostic and predictive significance of IL-1β expression in NSCLC across various molecular subtypes.
• To determine if IL-1β expression levels correlate with survival outcomes and treatment response in different NSCLC genetic profiles.

Main Methods:

• Analysis of 21,698 NSCLC tumors using DNA and RNA next-generation sequencing.
• Stratification of IL-1β expression into quartiles and assessment of real-world overall survival (OS) and time on treatment (TOT) using insurance claims data.
• Statistical analysis including Cox models to evaluate survival outcomes in relation to IL-1β expression and molecular alterations.

Main Results:

• Low IL-1β expression (Q1) was associated with longer OS in unselected NSCLC patients compared to high expression (Q4).
• This prognostic effect was more pronounced in EGFR-mutant adenocarcinoma and ALK fusion-positive NSCLC.
• High IL-1β expression correlated with longer time on immunotherapy in KRAS-mutant adenocarcinoma and was associated with TP53 mutations, high tumor mutational burden (TMB), and PD-L1 expression.

Conclusions:

• IL-1β expression serves as a potential prognostic and predictive biomarker in NSCLC, with significant associations in specific molecular subsets.
• IL-1β-targeted therapeutic strategies may hold particular promise for patients with EGFR- or ALK-altered NSCLC.
• Further research into the role of IL-1β in NSCLC pathogenesis and treatment response is warranted.