Helicobacter pyloriserology is associated with worse overall survival in patients with melanoma treated with immune checkpoint inhibitors

ABSTRACTThe microbiome is now regarded as one of the hallmarks of cancer and several strategies to modify the gut microbiota to improve immune checkpoint inhibitor (ICI) activity are being evaluated in clinical trials. Preliminary data regarding the upper gastro-intestinal microbiota indicated that Helicobacter pyloriseropositivity was associated with a negative prognosis in patients amenable to ICI. In 97 patients with advanced melanoma treated with ICI, we assessed the impact of H. pylorion outcomes and microbiome composition. We performed H. pyloriserology and profiled the fecal microbiome with metagenomics sequencing. Among the 97 patients, 22% were H. pyloripositive (Pos). H. pyloriPos patients had a significantly shorter overall survival (p = .02) compared to H. pylorinegative (Neg) patients. In addition, objective response rate and progression-free survival were decreased in H. pyloriPos patients. Metagenomics sequencing did not reveal any difference in diversity indexes between the H. pylorigroups. At the taxa level, Eubacterium ventriosum, Mediterraneibacter (Ruminococcus) torques, and Dorea formicigeneranswere increased in the H. pyloriPos group, while Alistipes finegoldii, Hungatella hathewayiand Blautia productawere over-represented in the H. pyloriNeg group. In a second independent cohort of patients with NSCLC, diversity indexes were similar in both groups and Bacteroides xylanisolvenswas increased in H. pyloriNeg patients. Our results demonstrated that the negative impact of H. pylorion outcomes seem to be independent from the fecal microbiome composition. These findings warrant further validation and development of therapeutic strategies to eradicate H. pyloriin immuno-oncology arena.