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J Can Res Metastasis, Volume 3
September 16-17, 2019 | Edinburgh, Scotland
Volume 3
Breast Cancer 2019 & Cancer Science 2019
September 16-17, 2019
Journal of Cancer & Metastasis Research
BREAST CANCER
CANCER SCIENCE AND THERAPY
2
nd
World Congress on
&
Conquer the tumor microenvironment: Phenotypic heterogeneity of human cancer
using imaging mass cytometry
Brenda B.G. Iglesias
Oncology Translational Medicines, UK
T
umours are highly heterogeneous populations of cells, and measures of intratumoral heterogeneity (ITH) and diversity
correlate with worse prognosis in many cancers. Emerging studies are highlighting functional interactions between subclones,
as well as among subclones and components of the tumour microenvironment. A growing body of evidence indicates that the
tumour microenvironment contributes to tumour growth and viability. However, these studies have focused on soluble factors
without interrogating the spatial distribution of subclones defined by activated signalling pathways. In large part, this is due to
limitations of currently available technology which does not allow for the detection of complex immunophenotypes in tissue
sections. High parameter methods such as gene expression profiling or flow cytometry have been applied to study the tumour
microenvironment (TME). However, data on cellular heterogeneity and rare cells is lost with gene expression studies, and the
spatial relationship between the tumour and immune cells is lost with flow cytometry. We will circumvent these limitations by
undertaking imaging mass cytometry (IMC), which allows for simultaneous measurement of 30-40 antigens while retaining
the spatial organization of the sample. Our objective is to develop and optimize highly multiplexed assays for characterization
of signalling heterogeneity in tissue microarrays of human tumours and describe the modelling cell signalling heterogeneity
in cell line-based models to determine mechanisms of cell-cell interaction and communication in various tumours on the IMC
platform. We have constructed an IMC panel of antibodies that combines markers for tissue architecture, tumour and immune
cell phenotyping, and signalling pathway activation. Analysis of individual tumours demonstrates unique compositions of cell
phenotypes between the edge and core of the tumour. Interestingly, while the tumour cells exhibit distinct phenotypes, the stromal
cells are largely indistinguishable from one another. Methods developed here should be applicable for the study of the TME in
different tumour types and could be used to identify additional biomarkers of response to immuno-oncology agents.
brendabeatriz.garcia@astrazeneca.com