Researchers at Wake Forest School of Medicine report that they have found biomarkers that indicate whether a patient will benefit from the use of immune checkpoint inhibitors (ICIs) to treat melanoma.
Melanoma is often curable if discovered and treated in its earliest stages, but when the disease progresses it can often spread quickly to other organs in the body and lead to death. And while ICIs have become an important treatment tool to tackle melanoma and other cancers, there is very little evidence of which patients will respond to this form of immunotherapy and which ones won’t.
“When immunotherapy works, it can be very successful and improve overall survival. About 20% to 40% of patients will respond,” said David R. Soto-Pantoja, Ph.D., associate professor of surgery and cancer biology who led the study. “But predictive biomarkers are urgently needed to guide treatment decisions and to develop new approaches to therapeutic resistance.”
For their research, published in the journal Clinical Cancer Research, the Wake Forest team analyzed blood samples from two different groups of patients before they have treatment, both groups had either stage III or stage IV melanoma. One group showed either a complete or partial response to ICI therapy, while the second group showed no positive response and exhibited disease progression.
Cancer cells consume abnormal nutrients and release factors that can be sensed by blood circulating cells. To better understand which patients responded and the extent of their immune response, the investigators delved into the bioenergetics or cellular metabolism of circulating immune cells called peripheral blood mononuclear cells and the metabolomic profiles of plasma.
Soto-Pantoja theorized it is possible that mitochondria of circulating cells can sense these metabolic changes and also examined how mitochondria change function in patients’ blood cells. “We found functional and molecular metabolic biomarkers, which are associated with ICI response, can be detected in blood before treatment,” Soto-Pantoja said.
The team found that the circulating immune cells of patients who responded to treatment had an increased extracellular acidification rate, a measure of glucose metabolism. Investigators also found changes in mitochondrial shape and structural changes linked to the response. In addition, responders to ICI treatment exhibited increased lactate levels to pyruvate (specific lipid and amino acid metabolites) and an elevated glucose receptor.
“Our study shows new insight in the treatment of melanoma that can be extended to other cancer types,” Soto-Pantoja said. “These biomarkers can potentially lead to personalized treatment strategies to improve overall survival.”
