Multiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometry

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dc.contributor.authorCarvajal-Hausdorf, Daniel
dc.contributor.authorPatsenker, Jonathan
dc.contributor.authorStanton, Kelly
dc.contributor.authorVillarroel-Espindola, Franz
dc.contributor.authorEsch, Amanda
dc.contributor.authorMontgomery, Montgomery
dc.contributor.authorPsyrri, Amanda
dc.contributor.authorKalogeras, Konstantine
dc.contributor.authorKotoula, Vassiliki
dc.contributor.authorFoutzilas, George
dc.contributor.authorSchalper, Kurt
dc.contributor.authorKluger, Yuval
dc.contributor.authorRimm, David
dc.date.accessioned2020-09-07T18:37:11Z
dc.date.available2020-09-07T18:37:11Z
dc.date.issued2019-05
dc.description.abstractPurpose: Imaging mass cytometry (IMC) uses metal-conjugated antibodies to provide multidimensional, objective measurement of protein targets. We used this high-throughput platform to perform an 18-plex assessment of HER2 ICD/ECD, cytotoxic T-cell infiltration and other structural and signaling proteins in a cohort of patients treated with trastuzumab to discover associations with trastuzumab benefit. Experimental design: An antibody panel for detection of 18 targets (pan-cytokeratin, HER2 ICD, HER2 ECD, CD8, vimentin, cytokeratin 7, β-catenin, HER3, MET, EGFR, ERK 1-2, MEK 1-2, PTEN, PI3K p110 α, Akt, mTOR, Ki67, and Histone H3) was used with a selection of trastuzumab-treated patients from the Hellenic Cooperative Oncology Group 10/05 trial (n = 180), and identified a case-control series. Results: Patients that recurred after adjuvant treatment with trastuzumab trended toward a decreased fraction of HER2 ECD pixels over threshold compared with cases without recurrence (P = 0.057). After exclusion of the lowest HER2 expressers, 5-year recurrence events were associated with reduced total extracellular domain (ECD)/intracellular domain (ICD) ratio intensity in tumor (P = 0.044). These observations are consistent with our previous work using quantitative immunofluorescence, but represent the proof on identical cell content. We also describe the association of the ECD of HER2 with CD8 T-cell infiltration on the same slide. Conclusions: The proximity of CD8 cells as a function of the expression of the ECD of HER2 provides further evidence for the role of the immune system in the mechanism of action of trastuzumab.es
dc.identifier.citationCarvajal-Hausdorf DE, Patsenker J, Stanton KP, et al. Multiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometry. Clin Cancer Res. 2019;25(10):3054-3062. doi:10.1158/1078-0432.CCR-18-2599es
dc.identifier.uridoi:10.1158/1078-0432.CCR-18-2599es
dc.identifier.urihttp://hdl.handle.net/11447/3412
dc.language.isoenes
dc.publisherAmerican Association for Cancer Research.es
dc.subjectHER2es
dc.subjectImmunohistochemistryes
dc.subjectT-celles
dc.subjectImaging mass cytometryes
dc.subjectMultiplexinges
dc.titleMultiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometryes
dc.typeArticlees

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