<i>Helicobacter pylori</i> serology is associated with worse overall survival in patients with melanoma treated with immune checkpoint inhibitors

Abstract

The 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 <i>Helicobacter pylori</i> seropositivity 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 <i>H. pylori</i> on outcomes and microbiome composition. We performed <i>H. pylori</i> serology and profiled the fecal microbiome with metagenomics sequencing. Among the 97 patients, 22% were <i>H. pylori</i> positive (Pos). <i>H. pylori</i> Pos patients had a significantly shorter overall survival (<i>p = .02</i>) compared to <i>H. pylori</i> negative (Neg) patients. In addition, objective response rate and progression-free survival were decreased in <i>H. pylori</i> Pos patients. Metagenomics sequencing did not reveal any difference in diversity indexes between the <i>H. pylori</i> groups. At the taxa level, <i>Eubacterium ventriosum, Mediterraneibacter (Ruminococcus) torques</i>, and <i>Dorea formicigenerans</i> were increased in the <i>H. pylori</i> Pos group, while <i>Alistipes finegoldii, Hungatella hathewayi</i> and <i>Blautia producta</i> were over-represented in the <i>H. pylori</i> Neg group. In a second independent cohort of patients with NSCLC, diversity indexes were similar in both groups and <i>Bacteroides xylanisolvens</i> was increased in <i>H. pylori</i> Neg patients. Our results demonstrated that the negative impact of <i>H. pylori</i> on outcomes seem to be independent from the fecal microbiome composition. These findings warrant further validation and development of therapeutic strategies to eradicate <i>H. pylori</i> in immuno-oncology arena.