CARVAJAL HAUSDORF, DANIEL EDUARDO
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CARVAJAL HAUSDORF, DANIEL EDUARDO
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dcarvajal@udd.cl
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56274228900

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

2019 , CARVAJAL HAUSDORF, DANIEL EDUARDO , Jonathan Patsenker , Kelly P. Stanton , Franz Villarroel-Espindola , Amanda Esch , Ruth R. Montgomery , Amanda Psyrri , Konstantine T. Kalogeras , Vassiliki Kotoula , George Foutzilas , Kurt A. Schalper , Yuval Kluger , David L. Rimm

Abstract Purpose: 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.

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Association of B7-H4, PD-L1, and tumor infiltrating lymphocytes with outcomes in breast cancer

2018 , Mehmet Altan , Kelley M. Kidwell , Vasiliki Pelekanou , CARVAJAL HAUSDORF, DANIEL EDUARDO , Kurt A. Schalper , Maria I. Toki , Dafydd G. Thomas , Michael S. Sabel , Daniel F. Hayes , David L. Rimm

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Objective measurement and clinical significance of IDO1 protein in hormone receptor-positive breast cancer

2017 , CARVAJAL HAUSDORF, DANIEL EDUARDO , Nikita Mani , Vamsidhar Velcheti , Kurt A. Schalper , David L. Rimm

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Expression and clinical significance of PD-L1, B7-H3, B7-H4 and TILs in human small cell lung Cancer (SCLC)

2019 , CARVAJAL HAUSDORF, DANIEL EDUARDO , Mehmet Altan , Vamsidhar Velcheti , Scott N. Gettinger , Roy S. Herbst , David L. Rimm , Kurt A. Schalper

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