Abstract
Simple SummaryAlthough immunotherapy has dramatically revolutionized non-small cell lung cancer (NSCLC) treatment, not all the patients will benefit from this innovative therapy. The identification of potential biomarkers able to predict efficacy and toxicity of immunotherapy represents an urgent need for tailored treatment regimens. Liquid biopsy is a minimally invasive and economical tool that could provide important information about patients’ selection and treatment monitoring. Currently, several blood biomarkers are under investigation (circulating immune and tumor cells, soluble immunological mediators, peripheral blood cells). Prospective clinical trials are needed to validate their use in clinical practice.Immune checkpoint inhibitors (ICIs) targeting the programmed cell death (PD)-1 protein and its ligand, PD-L1, and cytotoxic T-lymphocyte-associated antigen (CTLA)-4, have revolutionized the management of patients with advanced non-small cell lung cancer (NSCLC). Unfortunately, only a small portion of NSCLC patients respond to these agents. Furthermore, although immunotherapy is usually well tolerated, some patients experience severe immune-related adverse events (irAEs). Liquid biopsy is a non-invasive diagnostic procedure involving the isolation of circulating biomarkers, such as circulating tumor cells (CTC), cell-free DNA (cfDNA), and microRNAs (miRNAs). Thanks to recent advances in technologies, such as next-generation sequencing (NGS) and digital polymerase chain reaction (dPCR), liquid biopsy has become a useful tool to provide baseline information on the tumor, and to monitor response to treatments. This review highlights the potential role of liquid biomarkers in the selection of NSCLC patients who could respond to immunotherapy, and in the identification of patients who are most likely to experience irAEs, in order to guide improvements in care.
Highlights
Over recent years, the management of several tumors including non-small cell lung cancer (NSCLC) has been radically improved with the advent of immune checkpoint inhibitors (ICIs)
Assessment of programmed cell death protein ligand 1 (PD-L1) expression can be challenging in NSCLC patients, due to sampling problems, dynamic changes in programmed cell death (PD)-L1 expression over time, and intra-tumor spatial heterogeneity, implying that analyzed tumor tissue may not be indicative of the whole tumor microenvironment (TME) [8]
Pavan et al investigated the potential role of neutrophil to lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as predictors of immune-related adverse events (irAEs) in 184 advanced NSCLC patients treated with ICIs
Summary
The management of several tumors including non-small cell lung cancer (NSCLC) has been radically improved with the advent of immune checkpoint inhibitors (ICIs). These agents include antibodies targeting the programmed cell death receptor-1 (PD-1) (nivolumab, pembrolizumab, and cemiplimab), the anti-programmed death 1 ligand (PD-L1) (atezolizumab, durvalumab, and avelumab), and the cytotoxic. ICIs, most patients do not benefit from immunotherapy and eventually experience disease progression. Clinical trials have shown a positive association between PD-L1 expression on tumor tissue and tumor mutational burden (TMB), and disease response to immunotherapy [4]. Assessment of PD-L1 expression can be challenging in NSCLC patients, due to sampling problems (both techniques require adequate tissue biopsies), dynamic changes in PD-L1 expression over time, and intra-tumor spatial heterogeneity, implying that analyzed tumor tissue may not be indicative of the whole tumor microenvironment (TME) [8]
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