Immune checkpoint inhibitors (ICI) like anti-PD-1 antibodies are approved therapies for non-small cell lung cancer (NSCLC) treatment. Yet <50% of patients respond to treatment, revealing inadequacy of the leading prognostic biomarker, PD-L1. New biomarkers are thus critically needed to predict ICI response.
Our lab has developed methods to measure molecular profiles from liquid biopsy (blood draw)-derived circulating tumour cells (CTCs) and immune cells, using multiplexed immunofluorescence (IF). We can now image >50 markers in CTCs or immune cells - a world first that captures multi-faceted, high signal-to-noise (phospho)proteomic biomarker signatures with real potential to dramatically advance ICI-response prediction and monitoring. While 50 markers is >10 times the gold-standard in CTC imaging, it remains critical to select the right markers.
To guide selection, we will perform scRNAseq on a pilot cohort of NSCLC patients prior to ICI therapy, plus healthy donor controls. Transcriptomic analysis of immune and cancer cells will seek new biomarkers via comparative expression analyses, as well as employing state-of-the-art methods to predict immune-tumour interactions via ligand / receptor pair co-expression. We will test these predictions via multiplexed IF on paired samples to assess marker expression and localisation; establishing pilot data for new ICI predictive biomarker signatures.