Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer
Cell. 2023;186(2):363-381.e19. DOI 10.1016/j.cell.2022.12.028. PMID 36669472. PMCID PMC10019067.
How to cite
AMA
Lin JR, Wang S, Coy S, Chen YA, Yapp C, Tyler M, et al. Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer. Cell. 2023;186(2):363-381.e19. doi:10.1016/j.cell.2022.12.028APA
Lin, J. R., Wang, S., Coy, S., Chen, Y. A., Yapp, C., Tyler, M., et al. (2023). Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer. Cell, 186(2), 363-381.e19. https://doi.org/10.1016/j.cell.2022.12.028BibTeX
@article{lin2023multiplexed,
title = {Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer},
author = {Lin, Jia-Ren and Wang, Shu and Coy, Shannon and Chen, Yu-An and Yapp, Clarence and Tyler, Madison and others},
journal = {Cell},
year = {2023},
volume = {186},
number = {2},
pages = {363--381.e19},
doi = {10.1016/j.cell.2022.12.028},
pmid = {36669472}
}Solid tumors are tangled mixtures of cancer, immune, and structural cells, and the features pathologists use to grade them — how tumors bud, where immune cells gather — are usually judged from small tissue fragments. Whether those features are genuinely local, or thin slices through something much larger, was hard to know.
The team imaged 93 colorectal-cancer specimens with high-plex fluorescence microscopy and reconstructed one tumor in three dimensions from serial sections. Structures that look isolated in a single slice — tumor buds, mucin pools, and immune aggregates — turned out to be interconnected networks whose molecular states shift gradually rather than sharply.
The atlas reframes these diagnostic features as large-scale gradients and shows why whole-slide imaging, not small cores, is needed to measure them.
Key findings
- Whole-slide cyclic immunofluorescence resolved single cells across 93 colorectal tumors. High-plex CyCIF using panels of up to 102 antibodies imaged the full set of FFPE specimens, yielding roughly 200 million segmented single cells from 75 whole-slide images.
- Tissue-microarray cores proved too small to measure cell composition accurately. Because cells stay spatially correlated over roughly 80 to 400 microns, a 1-mm core of about 1,000 cells behaved as few as 1 to 3 independent samples, a 10- to 1,000-fold loss of statistical power that whole-slide imaging avoids.
- Diagnostic 2D features were in fact interconnected 3D structures. Reconstructing one tumor from serial sections showed that more than 900 lymphoid domains, each seemingly isolated in a single section, assemble into seven large three-dimensional networks spanning several millimeters.
CyteFinder in the methods
“Images were acquired using a 20x objective (0.75 NA) on a CyteFinder slide scanning fluorescence microscope (RareCyte Inc. Seattle WA).”
— Lin et al., Cell (2023), Methods, “CyCIF protocol”
Disclosure: RareCyte is named in the competing-interests statement of the publication cited above.
Why it matters for CyteFinder users
If you are weighing the CyteFinder for a tissue-imaging program, look at the scale it carried here. This was a whole-slide effort, not a tissue-microarray study, and that distinction is the paper's own argument: the authors show that 1-mm cores are too small to measure something as basic as cell abundance, because cells are spatially correlated over hundreds of microns. Answering the questions they cared about required imaging entire sections: where tumor buds sit, how immune cells organize at the invasive margin, whether tumor morphology is graded or discrete. The authors ran high-plex cyclic immunofluorescence on 93 FFPE colorectal specimens, acquiring each staining cycle on the CyteFinder and stitching the cycles into whole-slide images that together hold roughly 200 million single cells. From those images they typed cells, traced tumor-budding fibrils, and reconstructed tertiary-lymphoid-structure networks in three dimensions. For your own work the point is direct: when the biology lives at the scale of a whole specimen, whole-slide imaging is the measurement that captures it, and the CyteFinder is the instrument that produced these images.
