Characteristics of tumor microenvironment and novel immunotherapeutic strategies for non-small cell lung cancer

Immune checkpoint inhibitor-based immunotherapy has revolutionized the treatment approach of non-small cell lung cancer (NSCLC). Monoclonal antibodies against programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) are widely used in clinical practice, but other antibodies that can circumvent innate and acquired resistance are bound to undergo preclinical and clinical studies. However, tumor cells can develop and facilitate the tolerogenic nature of the tumor microenvironment (TME), resulting in tumor progression. Therefore, the immune escape mechanisms exploited by growing lung cancer involve a fine interplay between all actors in the TME. A better understanding of the molecular biology of lung cancer and the cellular/molecular mechanisms involved in the crosstalk between lung cancer cells and immune cells in the TME could identify novel therapeutic weapons in the old war against lung cancer. This article discusses the role of TME in the progression of lung cancer and pinpoints possible advances and challenges of immunotherapy for NSCLC.