Tumor-derived colorectal cancer organoids induce a unique Treg cell population through direct modulation of CD4+ T cell differentiation.
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ABSTRACT: To investigate the capacity for CRC tumor-organoids to influence Treg cell fate specification in vitro, we established a transwell co-culture model utilizing CD4+ T cells together with CRC tumor-organoids in which we study murine tumor-organoid induced Treg (mTO-iTreg) cell differentiation. As control, murine CD4+ T cells were cultured in transwell inserts and treated with TGFβ to induce Treg (TGFβ-iTreg) cells. To define the transcriptional identity of in vitro mTO-iTreg cells we performed bulk RNA-sequencing. RNA-sequencing analysis identified distinct transcriptional profiles between CRC organoid-induced Treg cells and TGFβ-induced Treg cells, with upregulation of key functional signature genes linked to CRC Treg cells in vivo. High expression of genes upregulated in CRC organoid-induced Treg cells correlates with shorter progression free intervaland overall survival of CRC patients, highlighting their prognostic potential.
ORGANISM(S): Mus musculus
PROVIDER: GSE272646 | GEO | 2024/12/19
REPOSITORIES: GEO
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