Microbiome Analysis to Predict Immunotherapy Response
University of Pittsburgh and National Cancer Institute researchers have identified key gut microbial signatures that could identify patients most likely to benefit from anti-PD-1 immune checkpoint blockade (ICB) immunotherapy. Microbiome analysis can predict progression free survival (PFS) and the occurrence of immune-related adverse events (irAEs). This analysis could be used to assist clinical decision making around treatment plans and lead to the development of personalized treatment for patients who do not respond to existing immunotherapy.
Description
Immunotherapy, where the body’s immune system fights cancer, has revolutionized the treatment of many cancers. One form of immunotherapy, anti-PD-1 ICB targets the programmed cell death protein 1 (PD-1) on the surface of T cells to prevent cancer cells suppressing T cell activity. However, most patients fail to respond to anti-PD-1 therapy and there is a pressing need to identify those patients who are most likely, or least likely to respond to therapy. Identifying patients least likely to respond to therapy or those most at risk of irAEs could inform treatment decisions. Recent research suggests the intestinal microbiome may predict response to anti-PD-1 therapy. Proof-of-concept studies demonstrated fecal microbiota transplantation from patients responding to anti-PD-1 therapy overcame treatment resistance and improved responsiveness in those who had previously not responded to anti-PD-1 therapy. Unique microbiome signatures associated with favorable and unfavorable outcomes have been identified and could aid treatment decision making and improve patient outcomes.Applications
• Melanoma• Lung cancers
• Other cancers treated using anti-PD-1 or other ICB treatments
Advantages
While some predictive biomarkers of ICB response have previously been reported, most patients are still not responding favorable to ICB therapy. Analysis of the microbiome from a large cohort of anti-PD-1 treated melanoma patients identified key taxonomic clades associated with either positive or negative outcomes in patients. Additionally, the presence of Streptococcus spp. or Lachnospiraceae spp. in the intestinal microbiome was linked with the adverse or favorable irAE related outcomes, respectively. This novel use of the intestinal microbiome as a tumor-extrinsic predictive biomarker could assist treatment decision making and may result in personalized therapy to those least likely to benefit from anti-PD-1 therapy.Invention Readiness
Stool sample analysis from five cohorts of patients treated with anti-PD-1 confirmed gut microbial signatures could predict response to treatment and outcomes from irAEs. Higher neutrophile-to-lymphocyte ratio, an indicator of systemic and gut inflammation, was negatively associated with poorer anti-PD-1 response.IP Status
https://patents.google.com/patent/WO2022261382A1Related Publication(s)
McCulloch, J.A., Davar, D., Rodrigues, R.R. et al. Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1. Nat Med 28, 545–556 (2022). https://doi.org/10.1038/s41591-022-01698-2