Biomarker Discovery in Patients with Immunotherapy-Treated Melanoma with Imaging Mass Cytometry.

Autor:	Martinez-Morilla S; Department of Pathology, Yale School of Medicine, New Haven, Connecticut., Villarroel-Espindola F; Department of Pathology, Yale School of Medicine, New Haven, Connecticut., Wong PF; Department of Pathology, Yale School of Medicine, New Haven, Connecticut., Toki MI; Department of Pathology, Yale School of Medicine, New Haven, Connecticut., Aung TN; Department of Pathology, Yale School of Medicine, New Haven, Connecticut., Pelekanou V; Department of Pathology, Yale School of Medicine, New Haven, Connecticut., Bourke-Martin B; Navigate BioPharma Services, Inc., Carlsbad, California., Schalper KA; Department of Pathology, Yale School of Medicine, New Haven, Connecticut., Kluger HM; Section of Medical Oncology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut., Rimm DL; Department of Pathology, Yale School of Medicine, New Haven, Connecticut. david.rimm@yale.edu.; Section of Medical Oncology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 Apr 01; Vol. 27 (7), pp. 1987-1996. Date of Electronic Publication: 2021 Jan 27.
DOI:	10.1158/1078-0432.CCR-20-3340
Abstrakt:	Purpose: Imaging mass cytometry (IMC) is among the first tools with the capacity for multiplex analysis of more than 40 targets, which provides a novel approach to biomarker discovery. Here, we used IMC to characterize the tumor microenvironment of patients with metastatic melanoma who received immunotherapy in efforts to find indicative factors of treatment response. In spite of the new power of IMC, the image analysis aspects are still limited by the challenges of cell segmentation. Experimental Design: Here, rather than segment, we performed image analysis using a newly designed version of the AQUA software to measure marker intensity in molecularly defined compartments: tumor cells, stroma, T cells, B cells, and macrophages. IMC data were compared with quantitative immunofluorescence (QIF) and digital spatial profiling. Results: Validation of IMC results for immune markers was confirmed by regression with additional multiplexing methods and outcome assessment. Multivariable analyses by each compartment revealed significant associations of 12 markers for progression-free survival and seven markers for overall survival (OS). The most compelling indicative biomarker, beta2-microglobulin (B2M), was confirmed by correlation with OS by QIF in the discovery cohort and validated in an independent published cohort profiled by mRNA expression. Conclusions: Using digital image analysis based on pixel colocalization to assess IMC data allowed us to quantitively measure 25 markers simultaneously on formalin-fixed, paraffin-embedded tissue microarray samples. In addition to showing high concordance with other multiplexing technologies, we identified a series of potentially indicative biomarkers for immunotherapy in metastatic melanoma, including B2M. (©2021 American Association for Cancer Research.)
Databáze:	MEDLINE
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