• Research shows that bacteria living in the intestines interact with the immune system.
• This study examined whether that interaction might affect how cancer patients respond to immune therapy.
• The study shows that the intestinal microbiome might signal whether immune therapy can help a patient.

COLUMBUS, Ohio – The intestinal microbiome might offer a window into whether cancer patients can benefit from immune therapy, according to a new study by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).

Immune therapy using drugs called checkpoint inhibitors has greatly improved survival for many cancer types. But not all patients with those cancers respond to the therapy, and biomarkers are needed to help doctors determine whether the treatment will likely be effective for a patient.

Research has shown that the intestinal microbiome interacts with the immune system, but how that interaction might affect immune checkpoint inhibitor (ICI) therapy is unknown.

This retrospective modeling study, published in the journal BMC Cancer, was undertaken to help answer that question and to learn if the microbiome might serve as a biomarker for immune checkpoint inhibitor (ICI) therapy success.

Using survival and other data from 690 patients with advanced cancer who were treated with immune checkpoint inhibitor (ICI) therapy and data from the medical literature, the researchers developed a model that related six medications taken by the patients for other conditions (e.g. comorbidities) and that affect the intestinal microbiome. They used the model to examine how these medicines might relate to survival after ICI therapy.

The model showed that medications expected to have significant impact on the microbiome were strongly associated with survival. Other drugs included in the study were proton pump inhibitors, histamine receptor blockers, non-steroid anti-inflammatories (NSAIDs) and statins.

“There is growing evidence that the microbiome can significantly influence immune checkpoint inhibitor therapy,” says first author Daniel Spakowicz, PhD, study first author and a member of the OSUCCC – James Molecular Carcinogenesis and Chemoprevention Program.

“If that’s true, our findings suggest that the microbiome might provide a marker for which patients will respond to the therapy.”

To conduct their study, the researchers did a literature search to identify cancers for which the microbiome might play a prognostic role. They then retrospectively analyzed the patients, all of whom received ICI therapy for advanced cancer at Ohio State’s James Cancer Hospital and Solove Research Institute between 2011 and 2017.

The researchers created a model to examine the relationship among patient characteristics, medications that affect the microbiome, inflammation and survival after ICI therapy.

The analysis controlled for patient variables such as age, performance status, comorbidities and body mass index. The researchers related these results to the microbes shown to be enriched or depleted in individuals who respond to immune checkpoint inhibitors.

“Combining these strategies added layers of support to define the role of the microbiome during ICI treatment for cancer, which is a rapidly evolving field in cancer immunology,” says Dwight Owen, MD, assistant professor in the Division of Medical Oncology and a member of the OSUCCC – James Translational Therapeutics Program. “Antibiotics and corticosteroids remained significantly associated with overall survival even when controlling for multiple factors such as performance status, comorbidities and stage.”

Key findings of the study include:

• Patients who took antibiotics or corticosteroids within 28 days of the start of ICI therapy showed reduced survival across all cancer types
• Beta-lactam antibiotics showed the strongest association with survival across all of the cancers tested.
• Other medications showed significant associations with specific cancers. For example, histamine receptor blockers and NSAIDs were associated with decreased survival in sarcoma and non-small cell lung cancer, respectively; protein pump inhibitors and statins were positively associated with overall survival in sarcoma.

“Our results strongly suggest that the microbiome plays an important role in response to immune checkpoint inhibitors, particularly in several cancers, but more work is needed to identify which microbes are important and solutions to mitigate these effects and perhaps promote greater response to ICIs,” says Spakowicz.

This project was supported by grants from the National Center for Advancing Translational Sciences (TR000090–05) and from the National Cancer Institute (CA016058–42).

Other Ohio State researchers involved in this study were Rebecca Hoyd, Mitchell Muniak, Marium Husain, James S. Bassett, Lei Wang, Gabriel Tinoco, Sandip H. Patel, Jarred Burkart, Abdul Miah, Mingjia Li, Andrew Johns, Madison Grogan, David P. Carbone, Claire F. Verschraegen, Kari L. Kendra, Gregory A. Otterson, Lang Li and Carolyn J. Presley.

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Media Contact: Amanda J. Harper
OSUCCC – James Media Relations
Direct Line: 614-685-5420
Central Media Relations: 614-293-3737
Amanda.Harper2@osumc.edu

*News release written by Darrell Ward.