Natural Killer Cells and Dendritic Cells: Expanding Clinical Relevance in the Non-Small Cell Lung Cancer (NSCLC) Tumor Microenvironment

SIMPLE SUMMARY: Cancer is one of the leading causes of mortality around the globe. In the past decades, there has been rapid progress in the development of tools to detect, screen, and treat several cancers. For its benefit to reach a wider patient population, significant challenges such as tumor heterogeneity, resistance to therapies, and lack of biomarkers should be addressed. The immune system holds the key to a greater understanding of these complex barriers. Natural Killer cells are cytotoxic cells of innate immunity that can kill multiple tumorigenic cells. Dendritic cells link innate and adaptive immunity by processing and presenting tumor-derived antigens to initiate anti-tumor T cell response. These immune cells and associated gene signatures have emerged as potential biomarkers with prognostic and predictive potential in several cancers. In this review article, we have discussed the biological roles of NK cells and DCs along with their translational relevance in NSCLC. ABSTRACT: Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer that accounts for almost 85% of lung cancer cases worldwide. Although recent advances in chemotherapy, radiotherapy, and immunotherapy have helped in the clinical management of these patients, the survival rate in advanced stages remains dismal. Furthermore, there is a critical lack of accurate prognostic and stratification markers for emerging immunotherapies. To harness immune response modalities for therapeutic benefits, a detailed understanding of the immune cells in the complex tumor microenvironment (TME) is required. Among the diverse immune cells, natural killer (NK cells) and dendritic cells (DCs) have generated tremendous interest in the scientific community. NK cells play a critical role in tumor immunosurveillance by directly killing malignant cells. DCs link innate and adaptive immune systems by cross-presenting the antigens to T cells. The presence of an immunosuppressive milieu in tumors can lead to inactivation and poor functioning of NK cells and DCs, which results in an adverse outcome for many cancer patients, including those with NSCLC. Recently, clinical intervention using modified NK cells and DCs have shown encouraging response in advanced NSCLC patients. Herein, we will discuss prognostic and predictive aspects of NK cells and DC cells with an emphasis on NSCLC. Additionally, the discussion will extend to potential strategies that seek to enhance the anti-tumor functionality of NK cells and DCs.