Riyue Bao, PhD, is a coauthor on the paper “The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients,” published in the January 5, 2018 issue of Science. In this paper, study director Thomas Gajewski, MD, PhD, and a team of UChicago scientists demonstrate that certain specific strains of commensal bacteria (the bacteria that live in the human digestive system, also know as the gut microbiome) in advanced melanoma patients are strongly correlated with a better response rate to immunotherapy drugs used to fight cancer.
Immunotherapy treatments, which harness the body’s own immune system to fight disease, are an active and growing area of cancer research, with new drugs approved in recent years and promising results in treating certain kinds of cancer. While immunotherapy has had success as a treatment for melanoma, only about 35 percent of those who receive such drugs have seen a significant benefit. Dr. Gajewski, the AbbVie Foundation Professor of Cancer Immunotherapy at the University, first identified the connection between specific gut bacteria and immunotherapy success rates in a November 2015 Science paper based on a mouse study.
His new study, which focused on 42 melanoma patients, involved collecting and analyzing the microbial makeup of stool samples from each patient prior to their receiving immunotherapy, and determining how the presence of various bacterial strains correlated with response to therapy. It also further tested the effects of both “good” and “bad” bacteria by introducing them to the intestines of mice, which were then implanted with melanoma cells and treated with an immunotherapy drug to study how the cancer’s growth and response to treatment were affected by the bacteria they received. The results of this study not only support the hypothesis that certain bacterial strains increase the success of immunotherapy, they show the effect of the microbiome to be even stronger than previously believed.
Riyue, a Research Assistant Professor in the Department of Pediatrics and the CRI’s Manager of Bioinformatics, conducted the analysis of microbiome and genomic data for this study. She analyzed microbiome data generated by 16S ribosomal amplicon sequencing and shotgun metagenomic sequencing, as well as genomics data generated by RNAseq and whole exome sequencing of tumor tissues. This analysis included detection of differential microbial composition between patient response groups, identification of bacterial species differentially abundant in responders or non-responders, and integration of multiple types of microbial and genomics data to identify molecular alterations associated with clinical outcome. In addition to the bioinformatics data, Riyue was also responsible for statistical analysis of the clinical data used in the study.
The paper was written by Dr. Gajewski in a highly collaborative process, with Riyue and other coauthors contributing revisions, comments, discussion, and methods. Riyue prepared figures and wrote the methods relevant to the bioinformatics analysis, including developing new approaches for the interpretation of the results.
This study has the potential to lead to more work that will deepen our understanding of which gut bacteria are harmful and helpful in cancer patients, as well as the mechanisms by which they work. This information can be integrated with existing methods to predict which patients will respond well to various treatments and allow doctors to tailor therapies based on their patients’ microbiomes, alongside other factors. It may also lead to trials of probiotic treatments that would introduce helpful bacteria as a way to potentially enhance the effects of immunotherapy.
Read more about the paper in The Forefront.