Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet

PD-L1 promoter methylation mediates the resistance response to anti-PD-1 therapy in NSCLC patients with EGFR-TKI resistance PD-L1 promoter methylation mediates the resistance response to anti-PD-1 therapy in NSCLC patients with EGFR-TKI resistance

Background. It has been known that there are microecology disorders during lung cancer development. Theoretically, intratumoral microbiota (ITM) can impact the lung cancer (LC) survival and treatment efficacy. This study conducted a follow-up investigation of non-small cell lung cancer (NSCLC) patients without lung infection to prove whether ITM indeed impacts the first-line treatment efficacy and survival. Methods. We enrolled all patients diagnosed with NSCLC in our department from 2017 to 2019, whose tumor samples were available (through surgery or biopsy) and sent for pathogen-targeted sequencing. All patients received the first-line treatment according to the individual situation. In the short term, the efficacy of the first-line treatment was recorded. During the follow-up, the survival status, progress events, and overall survival (OS) period were recorded if a patient was contacted. Results. Firstly, 53 patients were included, and our following analysis focused on the stage III and stage IV cases with ADC, SCC, or ASC tumors (47 cases). Several bacteria are associated with the LC status and progression, including N stages, metastasis sites, epidermal growth factor receptor (EGFR) mutation, first-line outcome, and later survival. The risk bacteria include Serratia marcescens, Actinomyces neesii, Enterobacter cloacae, and Haemophilus parainfluenzae; and the protective (against LC development and progression) ones include Staphylococcus haemolyticus and Streptococcus crista. In the logistic regression, the two-year survival can be predicted using the results of four bacteria (Haemophilus parainfluenzae, Serratia marcescens, Acinetobacter jungii, and Streptococcus constellation), with an accuracy rate of 90.7. Conclusion. ITM have links to malignancy, EGFR mutation, first-line outcome, and survival of NSCLC. Our results implied the potential anti-NSCLC activity of antibiotics when used reasonably. It is still necessary to deepen the understanding of the characteristics of ITM and its interactions with NSCLC tumors and the immune cells, which is significant in individualized approaches to the LC treatment.