Simultaneous Quantification of Multiple Immune Checkpoint Interactions in Melanoma

Area of Science:

• Oncology
• Immunology
• Biomarker Discovery

Background:

• Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but benefit only a subset of patients.
• Identifying biomarkers for the tumor immune microenvironment is crucial for clinical translation.
• Current methods face challenges in capturing dynamic, functional immune checkpoint interactions.

Purpose of the Study:

• To develop and apply a novel technology for quantifying functional immune checkpoint interactions.
• To assess the clinical relevance of immune checkpoint interaction profiling in ICI-treated patients.

Main Methods:

• Utilized amplified FRET-FLIM (QF-Pro®) technology for spatial and quantitative assessment of immune checkpoint interactions.
• Analyzed interactions in cells, FFPE tissues, and tumor samples.
• Quantified PD-1/PD-L1, CTLA-4/CD80, TIGIT/CD155, and LAG-3/MHC-II interactions.

Main Results:

• Robust quantification of four key immune checkpoint interactions (PD-1/PD-L1, CTLA-4/CD80, TIGIT/CD155, LAG-3/MHC-II) in FFPE samples.
• Observed patterns of concomitant engagement, with high PD-1/PD-L1 correlating with elevated CTLA-4/CD80.
• High LAG-3/MHC-II interaction status trended towards improved overall survival in melanoma patients treated with ICIs.

Conclusions:

• Immune checkpoint interaction profiling is a promising approach for patient stratification in immunotherapy.
• LAG-3/MHC-II engagement warrants further investigation as a potential predictive biomarker in melanoma.
• Prospective validation in larger cohorts is essential to establish clinical utility.