Single-cell RNA-Seq of colorectal cancer patient samples
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PROVIDER: EGAS00001006665 | EGA |
REPOSITORIES: EGA
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Project description:The response of naive CD8 T cells to acute infections results in the generation of defined yet heterogeneous pools of effector and memory cells. In contrast, the complexity of tumor infiltrating CD8 T cell states is still not fully elucidated. To delineate the landscape of tumor infiltrating CD8 T cells in an unbiased manner, we performed single-cell (full-length) RNA-Seq of CD8 T cells infiltrating mouse B16 melanomas. Our analysis of cell heterogeneity revealed the presence of multiple distinct CD8 T cell subtypes including exhausted, terminal effector, naive and memory-like CD8 T cells, as well as novel intermediate states. TCR reconstruction and pseudotime ordering enabled us to follow differentiation of single clones and suggested distinct trajectories towards T-cell exhaustion.
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Project description:The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated with increased IL-17 levels. In this study, we investigated the role of IL-17 in invasive breast tumor pathogenesis. We found that metastatic tumor-infiltrating T lymphocytes produced elevated levels of IL-17, whereas IL-17 neutralization inhibited tumor growth and prevented the migration of neutrophils and tumor cells to secondary disease sites. Tumorigenic neutrophils promote disease progression, and their depletion suppressed tumor growth. Moreover, IL-17 induced IL-6 and CXCL1 production in tumor cells, and IL-6 depletion reduced metastatic tumor growth and infiltration by Th17 cells and neutrophils. In addition, inoculation of a non-metastatic mammary tumor cell line pre-incubated with IL-17 promoted tumor growth, confirming the pro-tumor role of IL-17. Furthermore, high IL-17 expression was associated with lower disease-free survival (DFS) and worse prognosis in IDC patients. Thus, IL-17 blockade represents an attractive approach for the control of invasive breast tumors.
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