Soluble Biomarkers as Predictors of Response to Immunotherapy in Non-Small Cell Lung Cancer (NSCLC)-Insights from the Tumor Microenvironment Perspective

Lung cancer is the major cause of mortality worldwide with non-small cell lung cancer (NSCLC) contributing to 85% of the cases. FDA-approved immune checkpoint inhibitors (ICI), anti-PD-1, and anti-PD-L1 are widely used as a standard treatment. However, the response rate is limited and is observed in only 20–40% of the patients. Therefore, predictive and prognostic biomarkers are needed to help differentiate responders from non-responders, enabling a better understanding of disease dynamics and facilitating more effective management through the optimal use of these valuable drugs. In this context, tissue-based biomarkers have several limitations such as invasive sampling, tumor heterogeneity and difficulty in longitudinal monitoring. Therefore, non-invasive blood-based biomarkers could serve as impactful tools as predictive and prognostic biomarkers in ICI-treated NSCLC patients. In lieu of this, this review article aims to provide updated insights on the utility of soluble molecules such as soluble immune checkpoints, exosomes and cytokines as prognostic and predictive biomarkers of response in ICI-treated NSCLC patients.