Morphology-Driven, High-Plex Spatial Analysis of Immune Protein Expression in Lung Cancer

  • 9:30 am (PDT)
Speakers: David Rimm, MD, PhD, Yale University and Doug Hinerfeld, PhD, NanoString

Protein function within a tissue is regulated by both expression and location, and careful assessment of both is important to fully characterizing relevant tissue biology. Historically, the amount of information that could be obtained from a tissue sample was limited by single analyte assays that were non-quantitative, such as immunohistochemistry. Recent technological advances, such as multiplexed immunohistochemistry and quantitative immunofluorescence (QIF), have enabled quantitative characterization of multiple proteins within a single tissue, but these approaches are restricted to profiling a few markers at once and have limited dynamic range.

Digital Spatial Profiling (DSP) Technology developed by NanoString has the potential to overcome these challenges by utilizing oligo-barcoded antibodies and digital readouts to enable high multi-plexing of 800+ targets, with 40-plex for studies run to date, and greater dynamic range of up to 6 logs. We have tested DSP against QIF to evaluate the technical performance and observed high concordance across multiple protein markers. We have also utilized DSP to characterize immune infiltrates from tissue microarrays of defined cancer cohorts. Specifically, we have characterized immune markers within a cohort of lung tumors to identify differential patterns of immune protein expression that correlate with EGFR and/or KRAS mutation status.

Subsequently, we utilized DSP to identify potential prognostic signatures in lung cancers treated with an immune checkpoint inhibitor. These experiments demonstrate the potential for DSP to enable complex sample profiling and potentially construct new predictive signatures from cohorts with very limited tissue availability. 

FOR RESEARCH USE ONLY. Not for use in diagnostic procedures.