Lin, J.-R., Wang, S., Coy, S., Chen, Y.-A., Yapp, C., Tyler, M., Nariya, M. K., Heiser, C. N., Lau, K. S., Santagata, S., & Sorger, P. K. (2023). Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer. Cell, 186(2), 363-381.e13. doi: 10.1016/j.cell.2022.12.028
Advanced solid cancers, like colorectal cancer, are made up of tumor, immune, and supporting cells, all of which vary greatly within the tumor. In this study, we use advanced imaging techniques, 3D reconstruction, spatial statistics, and machine learning to identify the types and states of cells that contribute to important tumor features for diagnosis and prognosis. By analyzing these features with high-plex marker technology, we find patterns where tumor characteristics shift over time, some of which align with changes in genes and regulators that drive cancer. At the edge of the tumor, where cancer cells, normal cells, and immune cells interact, T cell suppression involves various cell types. Our 3D imaging shows that what appear to be small 2D features, like tertiary lymphoid structures, are often interconnected and show molecular changes across their area. This study suggests that while cancer genetics focus on specific changes in tumors, full-tissue imaging reveals larger-scale changes in both shape and molecules, similar to how tissues develop.
