Research News

A new Cleveland Clinic study identifies a surprising new driver of immunotherapy side effects: the skin microbiome.

The research, published in Cell Host & Microbe, includes first author Vanessa Salazar, an MD/PhD student in the lab of Thaddeus Stappenbeck, MD, PhD; and Anthony Fernandez, MD, PhD, a physician in Cleveland Clinic’s department of dermatology. Most existing research on side effects of immunotherapy in patients with cancer has focused on the gut bacteria as the cause—but targeting the gut also impacts the treatment’s effectiveness. While the team began their research project in the gut, they stumbled onto a connection with the skin. Their discovery suggests that the skin microbiome may be a new, practical target for reducing the side effects of immunotherapy without weakening cancer treatment.

What is the skin microbiome?

The skin microbiome is the community of microorganisms (like bacteria, viruses and fungi) living on the body. In addition to acting as protection from the outside world, the skin microbiome works with other parts of the skin to fight infection, heal wounds and aid the immune system.

Some cancer patients are given immunotherapy drugs (like checkpoint inhibitors) in combination with other treatments to help their immune systems attack tumors. These drugs disrupt the immune system and, for nearly half of these patients, can lead to side effects that are visible on the skin.

“It makes sense that the skin microbiome plays a more important role than we previously thought because skin reactions are typically the first to appear for patients—and most common,” Dr. Fernandez says. “Reactions range from mild rashes to severe autoimmune conditions and open lesions. In these more severe cases, the only solution is to stop immunotherapy altogether.”

A surprising discovery in the lab

During preclinical testing for a condition that involves the skin, Salazar discovered a new strategy that led to unexpected results: treatment with an antibiotic cream. She replicated the test (which yielded the same results) and then brought in Dr. Fernandez to help understand the immunopathologic skin findings and their implications.

“At first, I thought this was a mistake, but our team verified that topical antibiotics actually prevented further progression of disease,” Salazar says. “Our realization that the skin microbiome plays a larger role with immunotherapy than we thought is a reminder that discoveries can come from anywhere—and that in research, it’s important to study everything.”

Positive implications for future treatments

This study reveals that it may be easier to target the skin than the gut when helping patients manage adverse side effects from immunotherapy—particularly in severe cases where skin lesions appear. More importantly, the use of a topical antibiotic (as common as an antiseptic wash or steroid cream, both of which are used already for other conditions) will preserve the intended effects of the life-saving immunotherapies that some cancer patients need.

“Vanessa’s discovery, coupled with Tony’s validation from a physician’s perspective, show potential to easily translate this research into a clinical trial,” Dr. Stappenbeck says. “What we have found about the role of the skin microbiome suggests that when it comes to immunotherapy, it may be possible to separate the side effects from the benefits.”