Immunotherapy has revolutionized the treatment paradigm of non-small cell lung cancer
and improved patients’ prognosis. Immune checkpoint inhibitors have quickly become standard
frontline treatment for metastatic non-oncogene addicted disease, either as a single agent or in
combination strategies. However, only a few patients have long-term benefits, and most of them
do not respond or develop progressive disease during treatment. Thus, the identification of reliable
predictive and prognostic biomarkers remains crucial for patient selection and guiding therapeutic
choices. In this review, we provide an overview of the current strategies, highlighting the main
clinical challenges and novel potential biomarkers.