Cleveland Clinic awarded $12 million NIH grant to define how cytokines regulate inflammation

Cleveland Clinic's Lerner Research Institute was awarded a five-year $12 million grant by the National Cancer Institute, part of the National Institutes of Health, to define how cytokines - proteins produced during immune response - regulate inflammation and interact with cells and molecules surrounding tumors.

Delivering cytokines in immunotherapy can signal an immune response that kills off cancer cells, but resulting inflammation also can create an environment that encourages cells to mutate and tumors to grow. Gathering detailed information on how cytokines function within specific types of cancer can help navigate the complex pathways tumors use to evade treatment and make strategies like immunotherapy more successful.

Despite becoming more popular and holding significant potential, immunotherapies only work in a small portion of patients. We don't fully understand why they work in only 20-30% of patients with a particular type of cancer, and the other 70% don't respond. I think those differences are reflected in the complexity of this research."

Thomas Hamilton, Ph.D., director of Strategic Growth for Cleveland Clinic's Chief Research and Academic Office and primary investigator of the study

The NIH funding supports the next step in a decades-long research program at the Lerner Research Institute conducting groundbreaking research on cytokines, immune response and inflammation.

Primary investigators for the research program are long-time collaborators, including Dr. Hamilton, George Stark, Ph.D., Department of Cancer Biology in Lerner Research Institute; and Mark Jackson, Ph.D., Department of Pathology at Case Western Reserve University and Associate Director for Education and Training at the Case Comprehensive Cancer Center.

Researchers are examining cytokine effects within specific cancers. Drs. Stark and Hamilton investigate lung cancer, while Dr. Jackson's project concentrates on triple-negative breast cancer. Differentiating among different types of cancer is essential because treatments that work for one may not be effective in another, Dr. Stark says.

"Originally, cancers were categorized primarily by the organ in which they appeared," he says. "With molecular analyses, we now realize that there are many different subtypes for each cancer. We can optimize treatment for each individual cancer because we have a much better understanding of the underlying causes."

The program's results have the potential to translate directly into patient care, supporting Cleveland Clinic's approach to individualized and cutting-edge cancer treatments. "Identifying potential windows for therapy – specific cytokines, times, concentrations – all of those things might enable us to say antagonizing a specific factor or giving a specific treatment at a specific time can be beneficial," says Dr. Hamilton.

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