Melanoma, a kind of skin cancer, is usually treatable if caught and treated early on. The illness, on the other hand, can quickly spread to other organs in the body and become fatal. According to the American Cancer Society, more than 7,600 adults in the U.S. die of cancer each year.
Fortunately, immune checkpoint inhibitors (ICIs), a type of immunotherapy, have revolutionized the treatment of certain malignancies, including melanoma, and significantly improved patient care. But even though this immunotherapy is available, doctors haven’t been able to figure out who will benefit from it and who won’t.
Now, a group of Wake Forest School of Medicine researchers led by David R. Soto-Pantoja, Ph.D., associate professor of surgery and cancer biology, has uncovered blood biomarkers that may be used to predict patient response.
“When immunotherapy works, it can be very successful and improve overall survival. About 20% to 40% of patients will respond,” says the study author. “But predictive biomarkers are urgently needed to guide treatment decisions and to develop new approaches to therapeutic resistance.”
Blood samples from two patient groups, both with stage III and IV melanoma, were tested before therapy for the study. One group of patients experienced a complete or partial response to the ICI treatment. The disease progressed in the other group of patients who did not respond to ICI treatment.
The researchers looked at the bioenergetics or cellular metabolism of circulating immune cells known as peripheral blood mononuclear cells as well as the metabolomic profiles of plasma.
Cancer cells absorb aberrant nutrients and emit hormones that blood circulation cells can detect. According to the study authors, circulating cells’ mitochondria may be able to detect metabolic alterations. The team also looked into how this organelle affects blood cell function.
“We found functional and molecular metabolic biomarkers, which are associated with ICI response, can be detected in blood before treatment,” the authors added.
The extracellular acidification rate, a marker of glucose metabolism, was higher in the circulating immune cells of patients who responded to treatment. Changes in mitochondrial shape and structure were also connected to the response, according to the researchers. Increased lactate levels to pyruvate (particular lipid and amino acid metabolites) and a higher glucose receptor in individuals who reacted to treatment were also discovered to be a common metabolic profile that separated responders from non-responders.
“Our study shows new insight in the treatment of melanoma that can be extended to other cancer types,” the lead author said. “These biomarkers can potentially lead to personalized treatment strategies to improve overall survival.”
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