Elucidation of the interaction between gut microbiota and host immune system on NSCLC patients' response to immunotherapy.

The recent advances in immunotherapy have significantly changed the treatment landscape of NSCLC, which conventionally relies mainly on surgery, chemotherapy and radiotherapy. Currently, immune checkpoint inhibitors therapy is one of the first-line treatments for NSCLC patients. However, most of the NSCLC patients do not respond well to immunotherapy or develop primary resistance during the treatment. Hence, it is crucial to investigate the pathways driving patients’ response or resistance to immunotherapy. Recently, a new theory "gut-lung axis" is proposed to explain the communication between the lungs and gut. Gut dysbiosis is thought to influence the efficacy and patients' response to immunotherapy. It is believed that the gut microbiota composition will regulate the host epigenome and exerts their effects on patients' response to immunotherapy. Therefore, we will investigate the association between gut microbiota and host immune system, and their roles in influencing the NSCLC patients' response to immunotherapy in this study. Two groups of newly diagnosed NSCLC patients (respond well vs do not respond well to immunotherapy) will be recruited for this project, with strict inclusion criteria. Fecal and whole blood specimens will be collected from each study subject before and after immunotherapy. Bacterial DNA will be extracted from the fecal samples and subjected to 16S rRNA (V3-V4 region) metagenomic sequencing. Peripheral blood mononuclear cells (PBMC) will be isolated for the measurement of anti-tumour CD4+ and CD8+ T cells count, and IFN-γ and IL-2 level before and after the immunotherapy. Statistical analysis will be performed by using the Microsoft Excel and SPSS softwares. At the end of this study, we will be able to understand the relationship between gut microbiota and host immune system, and how these two components affecting the NSCLC patients’ response to immunotherapy.