Since its start in 2009, immunotherapy with immune checkpoint inhibitors has become a hot topic in respiratory oncology. Randomized controlled trials have proven the superiority of immune checkpoint inhibitor therapy versus standard chemotherapy in advanced non-small cell lung cancer (NSCLC). PD-L1 immunohistochemistry (IHC) is so far the most commonly implemented predictive biomarker in the selection of optimal candidates for immunotherapy. Immunotherapy with pembrolizumab is approved in first-line for advanced NSCLC with a PD-L1 expression on >50% of tumor cells, and after at least one prior chemotherapy regimen in case of PD-L1 expression of >1%. Treatment with nivolumab or with atezolizumab is approved for advanced NSCLC after prior chemotherapy, irrespective of the PD-L1 status. Since PD-L1 expression does not always correlate with treatment efficacy, other biomarkers are under investigation. Tumor mutational burden (which correlates clinically with smoking status) and CD8 tumor-infiltrating lymphocytes are associated with increased responsiveness to PD-L1 inhibition, and thus are other promising predictive biomarkers. NSCLC with molecular drivers on the contrary is preferably treated with tyrosine kinase inhibitors (TKIs) rather than immunotherapy due to lower response rates, even in case of high PD-L1 expression. Immunotherapy and other therapeutic modalities (chemotherapy, radiotherapy, TKIs) might work in synergy. The results of the first prospective trials with combination therapy were recently published, and many others are to be expected.
