Melanoma is often curable when detected and treated in its early stages. However, the disease can rapidly spread to other organs in the body and become deadly. Immune checkpoint inhibitors have transformed the treatment of certain cancers, including melanoma, and improved patient care.
But despite the availability of immunotherapy, physicians have been unable to predict who will benefit from immune checkpoint inhibitors and who will not. Now, a team of researchers has discovered blood biomarkers that can potentially predict patient response to immune checkpoint inhibition. Results from a recent study on the topic were published by Triozzi et al in Clinical Cancer Research.
“When immunotherapy works, it can be very successful and improve overall survival. About 20% to 40% of patients will respond,” said lead author David R. Soto-Pantoja, PhD, of Wake Forest School of Medicine. “But predictive biomarkers are urgently needed to guide treatment decisions and to develop new approaches to therapeutic resistance.”
Study Details
KEY POINTS
- The circulating immune cells of patients who responded to immune checkpoint inhibitor treatment had an increased extracellular acidification rate.
- Investigators also found changes in mitochondrial shape and structure changes that were linked to response.
- A common metabolic signature distinguished responders and nonresponders—an increased lactate-to- pyruvate ratio and an elevated glucose receptor in patients who responded to treatment.
For the study, scientists analyzed blood samples of two patient groups before treatment; both had stage III and IV melanoma. One group of patients responded to immune checkpoint inhibitor treatment and had a complete or partial response; the other patient group did not respond to immune checkpoint inhibitor treatment and had experienced disease progression.
The researchers examined the bioenergetics, or cellular metabolism, of peripheral blood mononuclear cells and the metabolomic profiles of plasma. Cancer cells consume abnormal nutrients and release factors that can be sensed by blood circulating cells. According to Dr. Soto-Pantoja, it’s possible that mitochondria of circulating cells can sense these metabolic changes. His team also examined how this organelle changes function in patients’ blood cells.
“We found functional and molecular metabolic biomarkers, which are associated with immune checkpoint inhibitor response, can be detected in blood before treatment,” Dr. Soto-Pantoja said.
The circulating immune cells of patients who responded to immune checkpoint inhibitor treatment had an increased extracellular acidification rate. Investigators also found changes in mitochondrial shape and structure changes that were linked to response. In addition, the team identified a common metabolic signature that distinguished responders and nonresponders—an increased lactate-to-pyruvate ratio and an elevated glucose receptor in patients who responded to treatment.
“Our study shows new insight in the treatment of melanoma that can be extended to other cancer types,” Dr. Soto-Pantoja said. “These biomarkers can potentially lead to personalized treatment strategies to improve overall survival.”
Disclosure: Funding for the study was provided by the V Foundation. For full disclosures of the study authors, visit aacrjournals.org/clincancerres.
