KEY TAKEAWAYS
- The study aimed to investigate soluble immune mediators and TME characteristics as predictors of response and survival in patients with NSCLC.
- Researchers noted that soluble immune mediators may predict survival in patients with NSCLC; further investigation is ongoing.
Despite the promising therapeutic efficacy of immune checkpoint inhibitor (ICI) monotherapy, most patients with non-small cell lung cancer (NSCLC) do not respond to this treatment. Therefore, determining which patients are likely to benefit most from ICI therapy remains a significant challenge.
Daiki Murata and the team aimed to identify soluble immune mediators and tumor microenvironment characteristics that could serve as biomarkers for predicting response and survival in patients with NSCLC undergoing ICI monotherapy.
They performed an inclusive analysis of 110 patients with advanced or recurrent NSCLC who received ICI monotherapy and had pre- and post-treatment plasma samples available. Among the 183 patients initially considered, 73 soluble immune mediators were measured at the initiation of ICI therapy and 6 weeks later.
The study analyzed the association between pre-treatment levels and on-treatment changes of these soluble immune mediators with patient survival. Additionally, the associations of these biomarkers with immune-related adverse event (irAE) development, PD-L1 expression, CD8+ TIL density, and neutrophil-to-lymphocyte ratio (NLR) were also evaluated.
In the study, univariate analysis revealed that pre-treatment biomarkers included 6 immune mediators, while on-treatment biomarkers included 8 immune mediators. Multivariate analysis identified 4 pre-treatment biomarkers (CCL19, CCL21, CXCL5, CXCL10) and 5 on-treatment biomarkers (CCL7, CCL19, CCL23, CCL25, IL-32).
The irAE development was associated with on-treatment changes in CCL23. PD-L1 expression correlated with pre-treatment levels of TNFSF13B and on-treatment changes in CCL25. The CD8+ TIL density was associated with pre-treatment CXCL10 levels, whereas the neutrophil to lymphocyte ratio (NLR) was correlated with pre-treatment levels of CCL13 and CCL17.
The study concluded that several soluble immune mediators serve as both pre-treatment and on-treatment biomarkers of survival in patients with NSCLC receiving ICI monotherapy. These biomarkers were also linked to potential predictors, such as irAE development, PD-L1 expression, CD8+ TIL density, and NLR.
The findings suggest that further large-scale studies are essential to confirm and establish these biomarkers in the treatment of patients with NSCLC.
This study was funded by AMED (Grant Number JP19ae0101076).
Source: https://pubmed.ncbi.nlm.nih.gov/39235457/
Murata D, Azuma K, Murotani K, et al. Characterization of pre- and on-treatment soluble immune mediators and the tumor microenvironment in NSCLC patients receiving PD-1/L1 inhibitor monotherapy. Cancer Immunol Immunother. 2024;73(11):214. Published 2024 Sep 5. doi:10.1007/s00262-024-03781-8
