Gut microbiota and clinical outcomes treated with nivolumab in Chinese non-small cell lung cancer.

Abstract

2614 Background: Gut microbiome affecting responses to immune checkpoint inhibitors (ICIs) against non-small cell lung cancer (NSCLC) has been investigated in western population. However, considering genetic variation, this phenomenon remains in vague in east-Asian NSCLC population. The study is designed to explore the relationships between gut microbiome and clinical outcomes treated with anti-PD-1 blockade in Chinese patients. Methods: 37 NSCLC patients received the treatment of Nivolumab were enrolled in the study from the clinical trials CheckMate870 (NCT03195491). Fecal samples were collected at the starting point, every time point performing clinical evaluation and that with disease progression. 16s sequencing was applied to assess the gut microbiota characteristics. Peripheral immune profiles were determined by multi-color flow cytometry in parallel. Results: When subgrouping patients into responders (R) and non-responders (NR) groups according to the clinical response assessed by RECIST1.1, patients in R group harbored higher diversity of gut microbiome at the starting point with consistent composition along the treatment. Analyzing progression-free survival (PFS) according to RECIST 1.1, patients with higher microbiome diversity had significantly prolonged PFS when compared to those with low diversity. Compositional difference was observed between two groups as well with the enrichment of Alistipes putredinis, Bifidobacterium logum, Prevotella corpri in R group whereas Ruminococcus_unclassified in NR group. Analysis of systemic immune responses using multi-color flow cytometry revealed that patients with a high abundance of microbiome diversity in the gut had more frequencies of memory CD8+ T cell subset in the periphery in response to anti-PD-1 therapy. Conclusions: Our results report the strong correlation between the gut microbiome diversity and the responses to anti–PD-1 immunotherapy in Chinese NSCLC patients regardless of genetic variation between Western and Chinese population. Patients with a favorable gut microbiome (such as high diversity) have enhanced immune responses mediated by effector T cell function in the periphery. These findings thus provide important implications for the prediction and the evaluation of anti-PD-1 immunotherapy against NSCLC.