Steven Ziegler, PhD, still has questions about a protein called thymic stromal lymphopoietin (TSLP) — even after studying it for more than 30 years. The Ziegler Lab helped establish that TSLP plays a role in asthma, lupus and several cancers. Now they are working to make sense of how and why this protein influences various diseases.

“TSLP is intriguing because it affects different cancers in different ways,” Dr. Ziegler says. “If TSLP is blocked in breast cancer, tumors shrink. But in melanoma, tumors grow.”

An exciting recent finding about TSLP’s role in colon cancer could open the door to new treatments and a better screening tool for this deadly disease.

Shrinking Tumors in Colon Cancer

Working with lab models and donated blood and tissue samples, the Ziegler Lab’s Kazushige Ninomiya, PhD, and his team discovered that the presence of TSLP made colon cancer worse. When they removed TSLP from the lab models, the tumors shrunk.

This finding provides hope for new ways to identify and treat colon cancer. This is especially important because only 5 percent of colon cancers respond to immune checkpoint inhibitor treatments that work well for other solid tumors.

Dr. Ninomiya also discovered a type of immune cell called a regulatory T cell (Treg) unique to colon cancer. Tregs are supposed to tell other immune cells to stop attacking when a threat to the immune system (like a virus or bacteria) is gone. But these Tregs seemed confused — they were telling the other immune cells not to attack cancer cells, effectively allowing them to grow.

“Since these Tregs are unique to colon cancer, we may be able to use them to create a new screening for the disease that doesn’t require a colonoscopy,” says Dr. Ninomiya. “Millions of Americans get colonoscopies every year, and they are expensive and invasive. We want to investigate whether a blood test to identify this cell would be a viable screening tool to create an easier, less expensive way to identify colon cancer.”

Further Exploring TSLP

The Ziegler Lab will investigate therapies that could target TSLP to slow colon cancer. They also plan to study immune cells and TSLP in pancreatic cancer with an eye toward better diagnostics and treatments for this deadly cancer.

“We’ve been on an incredible journey from understanding TSLP’s fundamental biology to better grasping the role it plays across several disease areas,” Dr. Ziegler says. “And yet, there’s still so much to learn. At this point nothing about this protein would surprise me.”

Fighting Diseases

September 15, 2022

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