American Association for Cancer Research
Browse

Supplementary Figure S6 from Biomarkers Associated with Beneficial PD-1 Checkpoint Blockade in Non–Small Cell Lung Cancer (NSCLC) Identified Using High-Plex Digital Spatial Profiling

Download (42.67 kB)
journal contribution
posted on 2023-03-31, 22:06 authored by Jon Zugazagoitia, Swati Gupta, Yuting Liu, Kit Fuhrman, Scott Gettinger, Roy S. Herbst, Kurt A. Schalper, David L. Rimm

Histogram showing CD3 counts (A) and CD8 counts (B) in the CD45 compartment (blue) and non-immune cells stromal compartment (orange) on each NSCLC case

Funding

Yale

Carlos III Research Institute

History

ARTICLE ABSTRACT

Only a minority of patients with advanced non–small cell lung cancer (NSCLC) truly benefits from single-agent PD-1 checkpoint blockade, and more robust predictive biomarkers are needed. We assessed tumor samples from 67 immunotherapy-treated NSCLC cases represented in a tissue microarray, 53 of whom had pretreatment samples and received monotherapy. Using GeoMx Digital Spatial Profiling System (NanoString Technologies), we quantified 39 immune parameters simultaneously in four tissue compartments defined by fluorescence colocalization [tumor (panCK+), leucocytes (CD45+), macrophages (CD68+), and nonimmune stroma]. A total of 156 protein variables were generated per case. In the univariate unadjusted analysis, we found 18 markers associated with outcome in spatial context, five of which remained significant after multiplicity adjustment. In the multivariate analysis, high levels of CD56 and CD4 measured in the CD45 compartment were the only markers that were predictive for all clinical outcomes, including progression-free survival (PFS, HR: 0.24, P = 0.006; and HR: 0.31, P = 0.011, respectively), and overall survival (OS, HR: 0.26, P = 0.014; and HR: 0.23, P = 0.007, respectively). Then, using an orthogonal method based on multiplex immunofluorescence and cell counting (inForm), we validated that high CD56+ immune cell counts in the stroma were associated with PFS and OS in the same cohort. This pilot scale discovery study shows the potential of the digital spatial profiling technology in the identification of spatially informed biomarkers of response to PD-1 checkpoint blockade in NSCLC. We identified a number of relevant candidate immune predictors in spatial context that deserve validation in larger independent cohorts.

Usage metrics

    Clinical Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC