▎WuXi AppTec content team editor
Colonoscopy and tissue sample screening are important means of preventing and diagnosing colorectal cancer, and although this method has been used for a long time, it still has certain limitations. After obtaining the sample, pathologists use staining to look at key structural features of the tissue and, if it is confirmed that the tissue is cancerous, to infer the stage of the cancer.
Peter Sorger, a professor of systematic pharmacology at Harvard Medical School, likens this approach to a blind man touching an elephant. In the latest study of Cell, Professor Soger and colleagues innovatively constructed a large-scale map of colorectal cancer, combining histology and single-cell imaging techniques, superimposing a large number of molecular information on histological features, and giving the first time that the whole picture of colorectal cancer was seen.
The results also overcome the limitations of traditional methods that cannot capture the molecular signature of cancer, and help more researchers obtain information that has been difficult to extract in the past few decades.
▲ Research to build a colorectal cancer map (Image source: Shannon Coy, Santagata lab)
According to the paper, the study used circulating immunofluorescence and multiplex imaging techniques, and about 100 million cells from tumor samples were imaged and analyzed. This high-definition analysis of the tumor allows researchers to see information that is normally overlooked.
Although the tumor as a whole has a strong ability to replicate and expand, the new study data shows a different picture: even a single tumor will have different partitions, some of which are more aggressive and some of which are weaker. In addition, some areas have stronger cancer characteristics, while others are relatively milder.
These differences also determine the histological structure of the tumor and also suggest the future development trend of the tumor.
The normal cells on the left in the atlas evolve towards the right cancer cells (Credit: Jia-Ren Lin, Sorger lab)
In addition to internal differences within the tumor itself, the immune system varies greatly within a single tumor and between different tumors. The study also found that the function of T cells responsible for fighting cancer is usually suppressed, but it has nothing to do with the tumor, and the source of the inhibition may be other immune cells in the microenvironment. This also suggests that identifying sensitive areas of the tumor before using immunotherapy may be better effective in removing the tumor.
In the atlas, the researchers also focused on a special class of structures, which they described as mucin pools. These mucin pools have various channel connections between them, and there are some protruding cancer cells. "These tumor structures had never been seen before, and now we can look at them in 3D." Professor Santagata said.
▲Schematic diagram of colorectal cancer map constructed by the study (Image source: Reference [2])
The research team pointed out that this part of the colorectal cancer map will advance cancer research and help improve existing treatments. They are also studying and mapping other cancer types, which will lay an important foundation for future precision cancer therapies.
Resources:
[1] An unprecedented look at colorectal cancer. Retrieved January 19th, 2023 from https://www.eurekalert.org/news-releases/976656
[2] Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer. Cell (2023). DOI: http://dx.doi.org/10.1016/j.cell.2022.12.028