Researchers have identified microbial signatures associated with outcomes of anti-PD-1 therapy in patients with melanoma, according to a study published in Nature Medicine.
The researchers noted that prior studies have linked the gut microbiome with outcomes of anti-PD-1 therapy, but these studies have produced inconsistent results.
For the current study, the researchers conducted a meta-analysis of microbial sequencing data from a new cohort (Pittsburgh cohort) and 4 previously published cohorts of melanoma patients treated with anti-PD-1 therapy.
The Pittsburgh cohort consisted of 94 patients. The researchers collected stool samples from 63 patients before the start of anti-PD-1 therapy or within 4 months of starting therapy (Pittsburgh early sample cohort [P-ESC]). The team also collected samples from 31 patients more than 4 months (range, 4-41 months) from the start of therapy (Pittsburgh late sample cohort [P-LSC]).
In the P-ESC cohort, patients who progressed on anti-PD-1 therapy had a distinct fecal microbiome signature compared with patients who did not progress. The baseline microbiota composition was most strongly associated with progression-free survival (PFS) at 9 to 10 months after the start of treatment (P =.006). In contrast, the fecal microbiome did not predict PFS in the P-LSC cohort.
Analyzing the Pittsburg cohorts and previously published cohorts together, the researchers identified bacteria associated with disease progression and non-progression.
Members of the Bacteroides genus and Proteobacteria phylum were associated with disease progression, but members of the Actinobacteria phylum and the Lachnospiraceae/Ruminococcaceae families of Firmicutes were associated with non-progression.
A microbial signature enriched for Lachnospiraceae spp. was associated with a favorable response to anti-PD-1 therapy, but a signature enriched for Streptococcaceae spp. was associated with an unfavorable response and distinct immune-related adverse events.
Patients with high Streptococcus spp. abundance had significantly shorter PFS than those with low Streptococcus spp. abundance (hazard ratio, 3.62; P =.0073).
“Our findings shed new light on the complex interaction between the gut microbiome and response to cancer immunotherapy, providing a roadmap for future studies,” the researchers wrote.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
McCulloch JA, Davar D, Rodrigues RR, et al. Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1. Nat Med. Published online February 28, 2022. doi:10.1038/s41591-022-01698-2