Immune Prophets of Lung Cancer: The Prognostic and Predictive Landscape of Cellular and Molecular Immune Markers.

Lung cancer is the leading cause of cancer deaths throughout the world. The majority of patients are diagnosed with locally advanced or metastatic disease when surgery, the best curative option, is no longer feasible. Thus, the prognosis of lung cancer remains poor and heterogeneous and new biomarkers are needed. As the immune system plays a pivotal role in cancer, the study of tumor microenvironment, with regard to the immune component, may provide valuable information for a better comprehension of the pathogenesis and progression of the disease. Through a detailed and critical evaluation of the most recent publications on this topic, we provide evidences of the prognostic and predictive significance of immune markers in tumor and in peripheral blood of lung cancer patients: from the landscape of immune cells (macrophages, neutrophils, lymphocytes and natural killer) and their cytokines, to the analysis of immune-checkpoints (PD-L1 and CTLA4), up to the genetic and epigenetic regulation of the immune response (immune gene signatures and miRNA). We also argue about the lights and shadows related to immune marker use in clinical practice, emphasizing on one hand the importance of their assessment in the choice of therapeutic treatment, on the other, the difficulty in their determination and reproducibility of literature data. The following review gives a foundation and a suggestion for future studies investigating tumor immunology in lung cancer.