Targeting Immune Determinants of Creating Tumor Heterogeneity in Lung Cancer

Lung cancer is the leading cause of cancer-related mortality. Lung tumors are composed of great complexity, including histological, genetic, and immunological diversity. A variety of agents have been clinically developed targeting the molecular mechanisms, including oncogenic driver gene mutations and immune checkpoint pathways. However, the clinical responses are limited to a small portion of the patients, and many patients finally acquire resistance to the treatment. Here, we provide an overview of the molecular and cellular mechanisms underlying the increase of tumor heterogeneity in lung cancer, and also of the clinical implementations for treating lung cancer. The histological types of lung cancer are divided into small-cell lung carcinoma and non-small-cell lung cancer. Which is further divided into adenocarcinoma, squamous cell carcinoma, large-cell carcinoma, and the subdivision. Genetic alterations of oncogenic drivers intrinsically generate a huge number of subclones, and the tumor heterogeneity is further epigenetically fostered by numerous immune components in the host. The reciprocal evolution between tumor cells and host immunity mutually raises the possibility of further tumor progression and metastasis leading to refractory cancer. Disruption of the tumor evolutional cascade by combining several agents that synergize well appears a promising strategy for better treating lung cancer. This review could contribute to better understanding of the molecular mechanisms underlying the refractoriness of lung tumors, and to conception of more effective treatments of lung cancer in clinical settings.