The National Institutes of Health has awarded a five-year grant of up to $3.2 million to researchers at the Keck School of Medicine of USC to further investigate the hormone thymulin and its role in chronic inflammation, known as 'inflammaging,' and cancer, according to an Aug. 4 announcement.
Thymulin is produced by the thymus, a small organ located behind the breastbone. Previous research from the Keck School of Medicine published in Nature Communications found that thymulin helps control chronic inflammation, which increases with age and weakens the body's ability to fight cancer. The same study reported that declining levels of thymulin are associated with rising inflammation and reduced immune response against cancer as people age.
The new NIH-funded project will explore whether thymulin can be used as an add-on treatment for older individuals undergoing immunotherapy for cancer, specifically therapies such as anti-PD-1 and anti-PD-L1 treatments. Researchers will also examine its potential for treating metastatic cancers through preclinical studies using aged mice with breast cancer or melanoma, along with tests on human cells in laboratory settings.
"By targeting one of the underlying drivers of inflammaging, we hope to help the immune system fight cancer more effectively, particularly in older individuals," said Ito, vice chair of basic and translational science in the Department of Surgery at USC.
In their earlier work published in Nature Communications, Ito's team demonstrated that thymulin reduced inflammation, improved survival rates, and enhanced immunotherapy effectiveness in older mice with cancer. The group identified thymulin as a key regulator linking inflammation with both cancer progression and response to immunotherapy. The new research aims to clarify how thymulin controls inflammation at a molecular level by studying signaling pathways and gene regulation in both mouse models and human cells.
Additional goals include investigating how thymulin alters immune activity within tumors—especially those unresponsive to current immunotherapies—and determining whether it can prevent or slow metastasis formation. Ito said most cancers develop later in life, but much existing knowledge about immunotherapy comes from studies on young animals: "To treat diseases of aging, we need models that reflect the biology of aging," he said. "Our goal is to make what we learn in the laboratory as relevant as possible to the patients most often affected by cancer."
