γδ T cell therapy for the treatment of non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality worldwide; more than one million people die every year (1). Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all cases and most patients with NSCLC are diagnosed at an advanced stage and have a poor prognosis, with a 5-year survival rate of <5%. Conventional treatment for this disease consists of surgery, radiotherapy, chemotherapy, and multimodality therapies. The patient’s cancer staging, histology, and tolerance including performance status and comorbidities used to determine the indication for the treatment. Recently, treatment decisions for NSCLC are driven by their tumour genotype or phenotype, such as mutations in epidermal growth factor receptor (EGFR) and the fusion oncogene EML4-ALK (2). Bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor-A, erlotinib and gefitinib, small molecule tyrosine kinase inhibitors (TKIs) that inhibit EGFR, and crizotinib, a TKI that inhibits EML4-ALK are widely used for the treatment. So-called “immune checkpoint blockade” T-cell modulating agents, such as antibodies against cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed death 1 (PD-1) and PD-L1, are currently being investigated. Despite the introduction of these new treatment modalities, outcomes remain poor, requiring for new treatment approaches. Active immunotherapy such as adoptive T cell-transfer represents one promising approach for lung cancer therapy (3). Growing body of evidence suggests that γδ T cells are attractive candidates for anticancer immunotherapy. This review discusses recent advances in basic γδ T cell research and data from clinical trials on the use of γδ Τ cells in the treatment of lung cancers