Emerging Blood-Based Biomarkers for Predicting Immunotherapy Response in NSCLC

Simple Summary Treatment with immunotherapy has been established as a standard treatment for lung cancer in recent years. Unfortunately, still, only a small proportion of patients benefit from the treatment, being the first leading cause of cancer death worldwide. Therefore, there is an urgent need for predictive biomarkers to help clinicians to discern whose patients are more likely to respond to immunotherapy. Since liquid biopsy opens the door to select patients and monitor the response during the treatment in a non-invasive way, in this review, we focus on the most relevant and recent results based on blood soluble biomarkers. Abstract Immunotherapy with Immune Checkpoint Inhibitors (ICIs) has demonstrated a profitable performance for Non-Small Cell Lung Cancer (NSCLC) cancer treatment in some patients; however, there is still a percentage of patients in whom immunotherapy does not provide the desired results regarding beneficial outcomes. Therefore, obtaining predictive biomarkers for ICI response will improve the treatment management in clinical practice. In this sense, liquid biopsy appears as a promising method to obtain samples in a minimally invasive and non-biased way. In spite of its evident potential, the use of these circulating biomarkers is still very limited in the real clinical practice, mainly due to the huge heterogeneity among the techniques, the lack of consensus, and the limited number of patients included in these previous studies. In this work, we review the pros and cons of the different proposed biomarkers, such as soluble PD-L1, circulating non-coding RNA, circulating immune cells, peripheral blood cytokines, and ctDNA, obtained from liquid biopsy to predict response to ICI treatment at baseline and to monitor changes in tumor and tumor microenvironment during the course of the treatment in NSCLC patients.