Effect of Nivolumab therapy on Metastatic Lung Cancer in Human Microbiome

Abstract

Nivolumab, a type of immunotherapy, has enhanced the 5-year survival of patients with renal cell cancer, melanoma, and lung cancer which is now mechanistically understood. However, relatively sparse information assesses its relationship with shaping the gut microbiome. We aimed to assess the degree to which nivolumab treatment contributes to alterations in the species composition of the colon in lung cancer patients undergoing nivolumab treatment. Our pilot study utilized stool samples of five lung cancer patients at Inland Hematology Oncology (IHO) before administration of nivolumab and three months after initiation of treatment. 16S and ITS rRNA sequence analysis were used to assess alterations in species abundance and richness of the colon. After sequencing, statistical analysis, specifically a paired t-test, was performed to assess if any significant differences in any microbial species were observed before and after immunotherapy treatment. Although different proportions of microorganisms existed at baseline prior to treatment for each patient, a significant reduction in the Megasphaera elsdenii population was observed (p=.0488; n=4), when comparing before and after treatment. Our findings differ from that of Huang et. al (2022), who has recently posited that a positive association exists between Megasphaera elsdenii and the survival of patients with pancreatic ductal adenocarcinomas. Our conclusions suggest that different cancers may elicit differential effects on Megasphaera elsdenii in the gut microbiome. ImportanceNivolumab is a relatively new form of cancer therapy called immunotherapy, which enables the body to use its own immune system to effectively fight cancer. Due to advances in microbial sequencing in 16S rRNA, this project explores differences in the abundance of microbial communities before and three months of treatment in patients who have advanced on chemotherapy. Our findings suggest that reduction of Megasphaera elsdenii, a metabolically active bacterium, is associated with positive outcomes, which differs from findings from other literature. Our project advocates for a more robust profiling of the microbiome during lung cancer treatment, and immunotherapy, in particular, to establish a more substantive profile of the changing gut in the midst of treatment.