High resolution mapping of the breast cancer tumor microenvironment using integrated single cell, spatial and in situ analysis of FFPE tissue
Abby Cutchin, Associate Director, Market Development, Oncology 10x Genomics
Bio: Abbey leads the oncology marketing team at 10x Genomics. Her team focuses on developing evidence for the use of single cell and spatial multiomics in emerging basic and translational cancer research applications. She leads several of 10x’s multi-institutional partnerships, including with the Parker Institute for Cancer Immunotherapy and Foundation for the NIH, as well as academic collaborations focused on immunotherapy and minimal residual disease. She received her degree in Bioengineering from Stanford, and currently lives in San Diego, California.
Abstract: At 10x Genomics, we provide single cell, spatial, and in situ technologies that fuel scientific discoveries. This presentation will explore how Chromium Single Cell, Visium Spatial, and Xenium In Situ platforms were applied to serial FFPE human breast cancer sections to uncover insights about disease progression. Integration of data from the three platforms across serial sections allowed us to identify three molecularly distinct tumor subtypes. We used Xenium to characterize cellular composition and differentially expressed genes within these subtypes. This analysis allowed us to draw biological insights about DCIS progression to infiltrating carcinoma, as the myoepithelial layer degrades and tumor cells invade the surrounding stroma.
AAnet identifies extreme cell states within a phenotypic cell state continue in primary and metastatic tumors
A/Prof Christine Chaffer, Strategic Program Lead - Precision medicine for cancer, Laboratory Head - Cancer Cell Plasticity Lab Garvan Institute
Bio: A/Prof Christine Chaffer is head of the Cancer Cell Plasticity lab at Garvan, and co-lead of the Precision Cancer Medicine Program. A/Prof Chaffer’s lab focuses on understanding how cancer cell plasticity – the ability of cancer cells to switch between different states – impacts tumour progression, metastasis and resistance to chemotherapy. Her immediate goal is to translate those research findings into new therapies to improve patient survival and quality-of-life.
Abstract: The emergence of heterogeneous cell states within a tumor is an adaptive process that fuels growth and metastasis, yet identifying biologically meaningful cell states and cell state structure remains a significant biological and computational challenge. For instance, neither clusters or trajectory models, which have been frequently used for deconvolving heterogeneity faithfully recapitulate the continuum structure seen in metastatic cancer. To address this, we develop Archetypal Analysis network (AAnet), a neural network that learns a latent simplicial representation of the data, where the vertices are idealized archetypal cell types and each cell is represented as a convex combination of these archetypes. We apply this method to an in vivo triple negative breast cancer model, and compare the heterogeneity of a primary tumor to those of several matched metastatic sites measured with single-cell RNA-sequencing. Deconvolving tumor heterogeneity in this way gives us archetypal states with dominant biological signatures including cell-proliferation, glycolytic metabolism and immune signalling. We then collect matched spatial RNA-seq data, which we analyze through another method that we developed called scMMGAN, revealing that several of the archetypes have distinct spatial patterns as well reflecting an archetypes unique biological function. In addition to primary tumors, we study several metastatic sites. Remarkably, we observe that this heterogeneity is nearly fully recapitulated in metastatic sites. We further show that the archetypal biological of the cancer cell states is reflected in the associated stromal cells, lending credence to the important contribution of micro-environmental and cancer cell cross-talk to overall archetypal biology. Together, the results demonstrate the ability of AAnet, together with multimodal single cell measurements,, to identify archetypal cell state heterogeneity and the underlying molecular programs defining primary and metastatic tumors
Victorian Cancer Biobank - a unique open-access resource for cancer research
Speaker: Dr. Wayne Ng, General Manager of VCB
Short presentation introducing the VCB followed by Q&A
Including presentation from
The Honourable Greg Hunt