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Soo Park, MD
Soo Park, MD
Posted: Wednesday, February 19, 2025
New research published in JCO Oncology Advances suggests that macrophage activity may be useful in predicting immunotherapy response among patients with melanoma. Amanda R. Kirane, MD, PhD, of Stanford University School of Medicine, California, and colleagues set out to examine novel biomarkers predicting patients’ likelihood of response to treatment with neoadjuvant talimogene laherparepvec, in which a modified oncolytic virus is injected directly into the melanoma to stimulate an immune response. Conventionally thought to work by stimulating T cells to attack cancer cells and shrink the melanoma, the researchers found no association between preexisting and posttreatment T-cell populations and treatment response. Rather, they found that differences in the macrophages themselves correlated with whether patients responded to the treatment.
“This study is highly informative in establishing a connection between preexisting innate immune functions and [the] ability to respond to immune-stimulating drugs,” said Dr. Kirane in a University of Bath press release. “It also strongly supports emerging evidence that there may be biological differences in patients more likely to respond to this kind of immunotherapy—oncolytic viruses—vs other types that target immune checkpoint regulators.”
Using tissue from a pilot phase II study of neoadjuvant talimogene laherparepvec before standard surgery, the investigators employed the immune time-resolved Förster resonance energy transfer (iFRET) technique to assess PD-L1/PD-1 interactions in the tumor immune microenvironment before and after therapy. They found that responsive tumors demonstrated significant increases in iFRET efficiency, and that changes in PD-L1/PD-1 iFRET efficiency did not correlate with changes in PD-L1 expression. In addition, the investigators reported that a tumor-associated macrophage phenotype correlated significantly with both response to treatment and the significantly high PD-L1/PD-1 interaction observed in the tumor beds of complete responders.
“The added information of iFRET-based immune activity measurements may offer the critical missing link of why current biomarkers have failed to yield a usable test to aid patients in treatment decision-making,” added Dr. Kirane.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
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