Top Line: The Human Tumor Atlas Network is a Cancer Moonshot initiative exploring the spatial and temporal evolution of cancer from development to metastasis.
The Study: A collection of papers was recently published describing several HTAN findings. This study examined 2D and 3D spatial structure of the tumor microenvironment (TME) and the interactions of cancer cells and normal cells with the TME from 131 tumors in 68 cases across 6 different cancer types. Within tumors, they identified tumor microregions surrounded by normal stroma. These microregions varied across tumor types, but generally primary tumors were composed of smaller microregions compared to metastases, which had more medium and large microregions. While microregions contained multiple spatially distinct genetic subclones, variation was also driven by proximity to the TME. Cells in the core of the microregion were often enriched for transcriptional programs involved in growth and metabolism. Cells near the periphery were more enriched for programs involved in invasion and immune modulation. Normal macrophages tended to cluster around the tumor edge, T cells infiltrated into the edges of microregions, and fibroblasts were the dominant normal cell type found in the inner core. There was also signaling back and forth between tumor cells and normal cells in the TME.
TBL: Studies such as these demonstrate that cancer is far more complex than we can often appreciate. As our understanding of this complexity evolves, so will the complexity of treatment necessary to make advances in patient outcomes. | Mo, Nature 2024
The Study: A collection of papers was recently published describing several HTAN findings. This study examined 2D and 3D spatial structure of the tumor microenvironment (TME) and the interactions of cancer cells and normal cells with the TME from 131 tumors in 68 cases across 6 different cancer types. Within tumors, they identified tumor microregions surrounded by normal stroma. These microregions varied across tumor types, but generally primary tumors were composed of smaller microregions compared to metastases, which had more medium and large microregions. While microregions contained multiple spatially distinct genetic subclones, variation was also driven by proximity to the TME. Cells in the core of the microregion were often enriched for transcriptional programs involved in growth and metabolism. Cells near the periphery were more enriched for programs involved in invasion and immune modulation. Normal macrophages tended to cluster around the tumor edge, T cells infiltrated into the edges of microregions, and fibroblasts were the dominant normal cell type found in the inner core. There was also signaling back and forth between tumor cells and normal cells in the TME.
TBL: Studies such as these demonstrate that cancer is far more complex than we can often appreciate. As our understanding of this complexity evolves, so will the complexity of treatment necessary to make advances in patient outcomes. | Mo, Nature 2024