Single-cell spatial mapping reveals alteration of cell type composition and tissue microenvironment during early colorectal cancer formation

Guha, T. K.; Esplin, E. D.; Horning, A. M.; Chiu, R.; Paul, K.; Weimer, A. K.; Becker, W. R.; Laquindanum, R.; Mills, M. A.; Esplin, D. G.; Shen, J.; Monte, E.; White, S.; Karathanos, T. V.; Cotter, D.; Bi, J.; Ladabaum, U.; Longacre, T. A.; Curtis, C.; Greenleaf, W. J.; Ford, J. M.; Snyder, M. P.

doi:10.1101/2024.11.20.622725

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bioRxiv · 10.1101/2024.11.20.622725

Single-cell spatial mapping reveals alteration of cell type composition and tissue microenvironment during early colorectal cancer formation

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Abstract

Familial adenomatous polyposis (FAP) is a rare, hereditary syndrome that raises the risk of developing colorectal cancer (CRC). This disease model is well suited for studying the early stages of malignant transformation. Our spatial CODEX experiments reveal that, in contrast to normal mucosa, FAP mucosa, pre-cancer polyps and colorectal cancers exhibit substantial alterations in the cell type composition and tissue microenvironment. These early alterations include: an increase in the population of cancer-associated fibroblasts (CAFs), and the inhibition of tumor infiltrated lymphocytes and cell-adhesion protein by CAFs, the transformation of memory T cells into regulatory T cells, nuclear translocation of beta-catenin from the cell membrane, a decrease in the M1:M2 macrophage ratio, a notable increase in angiogenesis events. Our studies define the early stem cell, stromal, and immune steps of colorectal cancer and may benefit early detection, and therapeutic intervention.

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Guha, T. K., Esplin, E. D., Horning, A. M., Chiu, R., Paul, K., Weimer, A. K., Becker, W. R., Laquindanum, R., Mills, M. A., Esplin, D. G., Shen, J., Monte, E., White, S., Karathanos, T. V., Cotter, D., Bi, J., Ladabaum, U., Longacre, T. A., Curtis, C., Greenleaf, W. J., Ford, J. M., Snyder, M. P.. 2024-11-21. Single-cell spatial mapping reveals alteration of cell type composition and tissue microenvironment during early colorectal cancer formation. https://doi.org/10.1101/2024.11.20.622725

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