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

Impact ofHelicobacter pyloriinfection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors

“…They further observed that this negative impact seemed to occur independently of fecal microbiome composition. 16 Finally, a smaller cohort of 77 patients with advanced gastric cancer (34 H. pylori- positive and 43 negative individuals) also demonstrated inferior PFS and OS outcomes for H. pylori- positive individuals. 17 …”

Cross-talk between Helicobacter pylori and gastric cancer: a scientometric analysis

“…Immunotherapy: Recent studies have shown that HP infection can adversely affect the tumor immune microenvironment and tumor immunotherapy. The overall survival (OS) and progression-free survival (PFS) of HP-positive cancer patients treated with immune checkpoint inhibitors, such as gastric cancer, melanoma and non-small cell cancer patients, were significantly reduced ( Che et al., 2022 ; Oster et al., 2022b ; Tonneau et al., 2022 ), but the specific mechanism is unknown. Some scholars have suggested that HP may reduce the efficacy of immunotherapy by changing the composition of intestinal flora and tumor immune microenvironment, affecting tumor immune response, but there is still a lack of relevant direct evidence ( Oster et al., 2022a ).…”

Intratumoural microbiota: a new frontier in cancer development and therapy

“… 7 Interestingly, previous research suggested that H. pylori infection is correlated with a favourable outcome in GC patients. 270 – 272 However, recent studies have indicated that the presence of H. pylori may affect the efficacy of ICIs in melanoma, 273 NSCLC, 274 and advanced GC, 275 introducing a new paradox regarding the varied effects of the same microorganism on cancer occurrence, prognosis, and treatment efficacy. Fungi also play a role in immunotherapy response in metastatic melanoma, with the Cladosporium genus significantly enriched in non-responders.…”