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Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front
Open accessAbstract
Antitumoral immunity requires organized, spatially nuanced interactions between components of the immune tumor microenvironment (iTME). Understanding this coordinated behavior in effective versus ineffective tumor control will advance immunotherapies. We re-engineered co-detection by indexing (CODEX) for paraffin-embedded tissue microarrays, enabling simultaneous profiling of 140 tissue regions from 35 advanced-stage colorectal cancer (CRC) patients with 56 protein markers. We identified nine conserved, distinct cellular neighborhoods (CNs)—a collection of components characteristic of the CRC iTME. Enrichment of PD-1 + CD4 + T cells only within a granulocyte CN positively correlated with survival in a high-risk patient subset. Coupling of tumor and immune CNs, fragmentation of T cell and macrophage CNs, and disruption of inter-CN communication was associated with inferior outcomes. This study provides a framework for interrogating how complex biological processes, such as antitumoral immunity, occur through concerted actions of cells and spatial domains.
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Cites
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Cited by
CD8+ T cell differentiation and dysfunction in cancer
Philip, M., & Schietinger, A. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-021-00574-3 · Cited by 1,052
Greenwald, N. F., Miller, G., Moen, E., Kong, A., Kagel, A., Dougherty, T., Fullaway, C. C., McIntosh, B. J., Leow, K. X., Schwartz, M. S., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-021-01094-0 · Cited by 953
Liver tumour immune microenvironment subtypes and neutrophil heterogeneity
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Spatially organized multicellular immune hubs in human colorectal cancer
Pelka, K., Hofree, M., Chen, J. H., Sarkizova, S., Pirl, J. D., Jorgji, V., Bejnood, A., Dionne, D., Ge, W. H., Xu, K. H., et al. (2021) · Cell · doi:10.1016/j.cell.2021.08.003 · Cited by 874
CODEX multiplexed tissue imaging with DNA-conjugated antibodies
Black, S., Phillips, D., Hickey, J. W., Kennedy-Darling, J., Venkataraaman, V. G., Samusik, N., Goltsev, Y., Schürch, C. M., & Nolan, G. P. (2021) · Nature Protocols · doi:10.1038/s41596-021-00556-8 · Cited by 659
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Metadata
- Authors
- Schürch, C. M., Bhate, S. S., Barlow, G. L., Phillips, D. J., Noti, L., Zlobec, I., Chu, P., Black, S., Demeter, J., McIlwain, D. R., Kinoshita, S., Samusik, N., Goltsev, Y., & Nolan, G. P.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 182
- Issue
- 5
- Pages
- 1341-1359.e19
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W3047081808
- Cited by
- 1,064
- References
- 20
- FWCI
- 33.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Schürch, C. M., Bhate, S. S., Barlow, G. L., Phillips, D. J., Noti, L., Zlobec, I., Chu, P., Black, S., Demeter, J., McIlwain, D. R., Kinoshita, S., Samusik, N., Goltsev, Y., & Nolan, G. P. (2020). Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front. Cell. https://doi.org/10.1016/j.cell.2020.07.005
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