HUMAN CANCER: In this study, multiplex immunofluorescence was used to analyze the staining patterns of 61 antigens on colon cancer samples from 747 patients. Results revealed tumor heterogeneity and offered the ability to map the TOR and MAPK pathways at the single-cell level. This data has served as a source for the development of analysis algorithms currently in use.*
Gerdes MJ, Sevinsky CJ, Sood A, et al. Highly multiplexed single-cell analysis of formalin-fixed, paraffin-embedded cancer tissue. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11982-7.
*Note that sophisticated analyses were not available at the time of publication. Single-cell segmentation then cluster analysis was performed. Visualization was done with in house
MOUSE STEM CELL: The Coffey lab at Vanderbilt University was an early adopter of Cell DIVE imaging in their work with mouse models to understand stem cell differentiation in the gut. This paper focuses on the tuft cell, a strange cell, which was mostly uncharacterized until this paper. Researchers used Cell DIVE to analyze tuft cell numbers in the small intestine and colon and found two new tuft cell markers. Then used physiological perturbations to characterize tuft cell phenotype.
McKinley ET, Sui Y, Al-Kofahi Y, et al. Optimized multiplex immunofluorescence single-cell analysis reveals tuft cell heterogeneity. JCI Insight. 2017 Jun 2;2(11). pii: 93487.
HUMAN CANCER, GLIOMA: This study used different modes of analysis, including genomic sequencing, magnetic resonance imaging (MRI), and multiplexed immunofluorescence, to better understand IDH1 mutant gliomas. These results demonstrate the utility of Cell DIVE in being paired with other modes of study to characterize tumor heterogeneity. Better tumor characterization can lead to an increased understanding of treatment response in genetically different gliomas.
Berens ME, Sood A, Barnholtz-Sloan JS, et al. Multiscale, multimodal analysis of tumor heterogeneity in IDH1 mutant vs wild-type diffuse gliomas. PLoS One. 2019 Dec 27;14(12):e0219724.
HUMAN METASTATIC CANCER: This paper examines the antitumor immune response, identifying homogenous and heterogenous cell patterns within the tumor microenvironment. This work resulted in the development of mathematic and spatial analysis tools with two algorithms to reveal cell interplay within the tumor microenvironment. A correlation between HLA-1 expression in the tumor and cytotoxic T lymphocyte infiltration into the tumor was observed. The use of Cell DIVE imaging in this study allowed for automated selection of regions of interest within the tumors for further analysis with other markers. Tumor microenvironment expression characteristics were found to be associated with patient outcomes. In the future this type of study is essential for the analysis of the response following immunotherapy.
Yan Y, Leontovich AA, Gerdes MJ, et al. Understanding heterogeneous tumor microenvironment in metastatic melanoma. PLoS One. 2019 Jun 5;14(6):e0216485.
HUMAN CANCER: This paper examines samples from relapsed thymoma and thymic carcinoma patients treated with avelumab. Two patients had a positive response and two had a partial response. All experienced adverse events when taking the drug. Cell DIVE imaging was used to characterize the tissues from patients with partial response (pre-treatment and post-treatment).
Rajan A, Heery CR, Thomas A, et al. Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (Avelumab) treatment in advanced thymoma. J Immunother Cancer. 2019 Oct 21;7(1):269.