H. Pylori May Hinder Efficacy of Immune Checkpoint Inhibitors

By Marilynn Larkin

July 29, 2021

NEW YORK (Reuters Health) - Helicobacter pylori decreased the efficacy of immune checkpoint inhibitors (ICIs) in mice and was associated with a less efficacious response to ICIs in a retrospective study of non-small-cell lung (NSCLC) cancer patients, researchers say.

"Several lines of evidence suggest that H. pylori actively suppresses functions of our immune system in order to establish chronic infection, through several mechanisms," Dr. Dominique Velin of the University of Lausanne in Switzerland told Reuters Health by email. "We hypothesized that the ICI-induced antitumor immune responses in H. pylori-infected patients might be less efficient as compared to those in non-infected patients."

"Our initial results suggest that the stomach microbiota affects the response to cancer immunotherapies and that H. pylori serology may be of use to personalize cancer immunotherapy in patients with NSCLC," he said. "These preliminary results will have to be confirmed in larger prospective cohorts, including patients with NSCLC and other types of cancer."

As reported in Gut, Dr. Velin and colleagues assessed whether ICIs or vaccine-based immunotherapies are effective in reducing tumor volumes in H. pylori-infected mouse models of colon cancer and melanoma compared to non-infected mice.

Tumor volumes of non-infected mice undergoing anticytotoxic T-lymphocyte-associated protein 4 and/or programmed death ligand 1 (PD-1) or anti-cancer vaccine treatments were significantly smaller than those of infected mice.

Further, infected mice treated with cancer immunotherapies had fewer activated tumor-specific CD8+ T cells in their tumors, regardless of the overall composition of their gut microbiome.

In addition, an in vitro co-culture assay revealed that dendritic cells in infected mice promote lower tumor-specific CD8+ T cell proliferation.

The team also reviewed the correlation between H. pylori seropositivity and the efficacy of PD-1 blockade therapy in NSCLC patients in two independent cohorts. In one cohort, H. pylori seropositivity was associated with decreased survival on anti-PD-1 therapy: median survival for H. pylori seropositive patients was 6.7 months versus 15.4 months for seronegative patients.

In the other cohort, H. pylori seropositivity was associated with an "apparent" decrease in progression-free survival on anti-PD-1 therapy.

The authors conclude, "Our study unveils for the first time that the stomach microbiota affects the response to cancer immunotherapies and that H. pylori serology would be a powerful tool to personalize cancer immunotherapy treatment."

Surgical oncologist Dr. Andrea Porpiglia, an assistant professor at Fox Chase Cancer Center in Philadelphia commented in an email to Reuters Health, "The results seem promising as one factor that cancer patients may not respond to immunotherapy. The role of H. pylori infection influencing cancer immunotherapies needs to be further investigated in humans as there are numerous different immunotherapies available in numerous different cancers."

SOURCE: https://bit.ly/3BO7GfT Gut, online July 12, 2021.