Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer

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Single-cell RNA sequencing of colorectal tumors highlights associations between lineage-related gene expression signatures and specific stromal and immune cell populations. Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,103 unsorted single cells from 23 Korean and 6 Belgian patients. Cancer cells displayed transcriptional features reminiscent of normal differentiation programs, and genetic alterations that apparently fostered immunosuppressive microenvironments directed by regulatory T cells, myofibroblasts and myeloid cells. Intercellular network reconstruction supported the association between cancer cell signatures and specific stromal or immune cell populations. Our collective view of the cellular landscape and intercellular interactions in colorectal cancer provide mechanistic information for the design of efficient immuno-oncology treatment strategies.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2020-06
Language
English
Article Type
Article
Citation

NATURE GENETICS, v.52, no.6, pp.594 - +

ISSN
1061-4036
DOI
10.1038/s41588-020-0636-z
URI
http://hdl.handle.net/10203/279565
Appears in Collection
BiS-Journal Papers(저널논문)
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