Advancing Precision Immunotherapy for Stage II Melanoma - European Medical Journal Advancing Precision Immunotherapy for Stage II Melanoma - AMJ

Advancing Precision Immunotherapy for Stage II Melanoma

A RECENT study has uncovered promising advancements in the fight against Stage II melanoma by introducing a novel biomarker technique, immune Förster resonance energy transfer (iFRET). This cutting-edge diagnostic tool, developed as part of a pilot Phase II study, holds the potential to revolutionize how healthcare professionals evaluate the efficacy of neoadjuvant immunotherapy.

The study examined the tumor immune microenvironment (TiME) of patients undergoing treatment with talimogene laherparepvec (TVEC), an oncolytic virus therapy administered before surgery. Researchers used iFRET to measure PD-L1:PD-1 checkpoint interactions in the tumor tissue both pre- and post-treatment. They discovered that iFRET efficiency was significantly higher in tumors that responded positively to TVEC compared to nonresponding tumors, which either exhibited reduced checkpoint engagement or no measurable immune stimulation.

Traditional biomarkers such as PD-L1 expression and T-cell phenotyping failed to align with therapeutic outcomes due to notable heterogeneity across and within tumors. Instead, the findings highlighted the importance of tumor-associated macrophages (TAMs). High PD-L1:PD-1 interaction levels in TAMs were strongly associated with complete treatment responses, underscoring the critical role of innate immune profiles in determining therapy success.

This research demonstrates how iFRET could become a companion diagnostic tool, enabling personalized therapeutic strategies for patients with melanoma. By providing dynamic, functional insights into checkpoint activity, iFRET addresses the limitations of existing static biomarkers and emphasizes the need for refined approaches in ongoing clinical trials.

Reference: Kirane AR et al. Toward Functional Biomarkers of Response to Neoadjuvant Oncolytic Virus in Stage II Melanoma: Immune-Förster Resonance Energy Transfer and the Dynamic Tumor Immune Microenvironment. JCO OA. 2025;2.

Anaya Malik | AMJ

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