Touching (Proximity) as a Companion Diagnostic Test

This article discusses a promising diagnostic approach aimed at improving patient selection for immune checkpoint inhibitor (ICI) therapies, particularly in non-small cell lung cancer (NSCLC). The current reliance on PD-L1 immunohistochemistry (IHC) as a biomarker has limited sensitivity and specificity. The concept of “touching” refers to the direct molecular interaction between PD-1 and PD-L1 proteins, which can be detected through proximity-based assays such as proximity ligation assay (PLA), Förster resonance energy transfer (FRET), and quantitative immunofluorescence (QIF). The authors highlight new evidence showing that higher PD-1/PD-L1 proximity scores—measured using second-generation PLA—correlate with better treatment responses and survival in ICI-treated patients with NSCLC.  This article is important to the cardiothoracic surgery and thoracic oncology communities, including CTSNet’s global audience, as it signals a potential paradigm shift in how surgical candidates for immunotherapy are selected. As immunotherapy becomes increasingly integrated into multimodal treatment, improved predictive biomarkers such as proximity assays could enhance personalized treatment strategies.