Natural Killer Cells in Cancers of Respiratory System and Their Applications in Therapeutic Approaches

Background: Cancer is still regarded as a major worldwide health issue due to its high health and socioeconomic burden. Currently, lung cancer is the most common cause of cancer-related fatalities globally. Additionally, mesotheliomas and other cancers of the respiratory system, including those of the trachea, larynx, and bronchi, are also posing a significant health threat. Natural killer (NK) cells are lymphocytes of the innate immune system involved in response against cancer.

Objective: This review discussed recent findings in the context of NK cell activity in the immune surveillance of respiratory system cancers and NK cell-based treatments to combat those malignancies.

Results: The presence of natural killer cells in the tumor microenvironment is shown to be associated with a higher survival rate in patients with various malignancies. However, cancerous cells benefit from several mechanisms to evade natural killer cell-mediated cytotoxicity, including reduced major histocompatibility complex I expression, shedding of ligands, upregulation of inhibitory receptors, and release of soluble factors. Using NK cells to design therapeutic approaches may enhance antitumor immunity and improve clinical outcomes. Clinical trials investigating the use of natural killer cells in combination with cytokine stimulation or immune checkpoint inhibitors have exhibited promising results in various respiratory system malignancies.

Conclusion: Respiratory system cancers present significant health challenges worldwide, and while NK cells play a crucial role in tumor surveillance, tumors often evade NK cell responses through various mechanisms. Advances in NK cell-based therapies, including CAR-NK cells, immune checkpoint inhibitors, and cytokine stimulation, have shown promising outcomes in tackling these tactics. However, challenges such as the immunosuppressive tumor microenvironment persist. Ongoing research is crucial to improve NK cell therapies by targeting autophagy, modulating miRNAs, and developing combinatorial approaches to enhance treatment efficacy for respiratory cancers.