Researchers identify biomarkers to predict patient response to
immunotherapy treatment for melanoma

Date:
February 17, 2022
Source:
Wake Forest Baptist Medical Center
Summary:
A team of researchers has discovered blood biomarkers that can
potentially predict patient response in the treatment of melanoma.



FULL STORY ========================================================================== Melanoma, a type of skin cancer, 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. According to the American
Cancer Society, more than 7,600 people die of the disease each year in
the United States.


========================================================================== Thankfully, immune checkpoint inhibitors (ICI), a type of immunotherapy,
have transformed the treatment of certain cancers, including melanoma, and improved patient care. But despite the availability of this immunotherapy, doctors have been unable to predict who will benefit from ICI and who
will not.

Now, a team of researchers at Wake Forest School of Medicine, led by
David R.

Soto-Pantoja, Ph.D., associate professor of surgery and cancer biology,
has discovered blood biomarkers that can potentially predict patient
response.

Results from the study are published online in Clinical Cancer Research,
a journal of the American Association for Cancer Research.

"When immunotherapy works, it can be very successful and improve overall survival. About 20% to 40% of patients will respond," Soto-Pantoja
said. "But predictive biomarkers are urgently needed to guide treatment decisions and to develop new approaches to therapeutic resistance."
For the study, scientists analyzed blood samples of two patient groups
before treatment, both with stage III and IV melanoma. One group of
patients responded to ICI treatment and had a complete or partial
response. The other patient group did not respond to ICI treatment and
had disease progression.

Scientists examined the bioenergetics or cellular metabolism of
circulating immune cells called 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 Soto-Pantoja, it's
possible that mitochondria of circulating cells can sense these metabolic changes. Soto- Pantoja's team also examined how this organelle changes
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 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 structure
changes that were linked to the response. In addition, the team
identified a common metabolic signature that distinguished responders
and non-responders - - increased lactate levels to pyruvate (specific
lipid and amino acid metabolites) 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," Soto-Pantoja said. "These biomarkers can potentially lead to personalized treatment strategies to improve overall survival." Funding for the study was provided by the V Foundation
V Scholar in Cancer 519 Research Award No. V2019-018 and NCI Grant
No. P30CA012197.

========================================================================== Story Source: Materials provided by
Wake_Forest_Baptist_Medical_Center. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Pierre L. Triozzi; Elizabeth R. Stirling; Qianqian Song; Brian
Westwood;
Mitra Kooshki; M. Elizabeth Forbes; Beth C. Holbrook; Katherine
L. Cook; Martha A. Alexander-Miller; Lance D. Miller; Wei Zhang;
David R. Soto- Pantoja. Circulating Immune Bioenergetic, Metabolic,
and Genetic Signatures Predict Melanoma Patients' Response to
Anti-PD-1 Immune Checkpoint Blockade. Clinical Cancer Research,
2022 DOI: 10.1158/1078- 0432.CCR-21-3114 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220217102023.htm

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