MAY 19, 2020 11:45 AM EDT | APAC MAY 20, 2020 2:45 PM CST

Discovery of Biomarkers Associated with Benefit From PD-1 Checkpoint Blockade in Non-small-cell Lung Cancer (NSCLC) Using High-plex Digital Spatial Profiling

Speaker
  • Physician Scientist, Department of Medical Oncology, Lung Cancer Unit
    Biography
      I am a physician-scientist focused in lung cancer. I earned an MD degree from the University of Navarra School of Medicine (2007) and I was trained as a resident in medical oncology at Hospital Clinico San Carlos in Madrid (2008-2012). I attained a Ph.D. degree in 2014 working in predictors of BRCA1/2 mutations in women with early-onset breast cancer. I gained extensive training in the methodology of clinical research in lung cancer under the supervision of Luis Paz-Ares (2015-2017). In 2017, I moved to the prestigious laboratory of Dr. Rimm at Yale (New Haven, USA) as a post-doctoral scientist, where I acquired expertise in immunotherapy biomarker science and immunobiology. In 2019, I moved back to my home institution in Madrid (Hospital 12 de Octubre) as a faculty member and independent investigator. My research interests are focused on biomarker science and development of precision immunotherapy strategies for patients with lung cancer.

    Abstract

    The majority of patients with advanced NSCLC do not respond to monotherapy with PD-1 axis inhibition, and more robust predictive biomarkers are needed. In this study, we assessed tumor samples from 67 immunotherapy-treated NSCLC cases represented in a tissue microarray, 53 of whom had pre-treatment samples and received monotherapy. Using GeoMx Digital Spatial Profiling (DSP) system (NanoString), we quantified 39 immune parameters simultaneously in four tissue compartments defined by fluorescence co-localization (tumor [panCK+], leucocytes [CD45+], macrophages [CD68+], and non-immune stroma). In the univariate unadjusted analysis, we found 18 markers associated with outcome in spatial context, 5 of which remained significant after multiplicity adjustment and after controlling for clinical confounding factors. In the multivariate analysis, high expression of CD56 and CD4 in the CD45 compartment were significantly associated with all favorable clinical outcomes, whereas high levels of VISTA and CD127 in the tumor compartment were markers associated with immunotherapy resistance. We also validated the DSP finding that high CD56+ immune cell counts in the stroma were predictive for PFS and OS in the same set of patients using multiplex immunofluorescence, strengthening the relevance of NK/NKT cells


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