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

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Daniel E Carvajal-HausdorfDavid L Rimm

Abstract

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. 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. 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 immunofluoresc...Continue Reading

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Citations

Jan 22, 2020·Nature·Hartland W JacksonBernd Bodenmiller
Dec 5, 2019·Frontiers in Immunology·Heeva BaharlouEllis Patrick
Oct 16, 2020·Brain Pathology·Camila Fernández-ZapataChotima Böttcher
Jan 29, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sandra Martinez-MorillaDavid L Rimm
May 22, 2021·Chemical Reviews·Philip A DobleDavid Clases
May 30, 2020·Trends in Cancer·Shuangyi CaiAhmet F Coskun
Aug 27, 2021·Cancer Immunology Research·Nicolas A GiraldoJanis M Taube

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