Fungal mycobiome drives IL33 secretion and type 2 immunity in pancreatic cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA785869 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17116076.fastq.gz | Fastqsanger.gz | |||
| SRR17116077.fastq.gz | Fastqsanger.gz | |||
| SRR17116078.fastq.gz | Fastqsanger.gz | |||
| SRR17116079.fastq.gz | Fastqsanger.gz |
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Project description:TH2 and innate lymphoid cells 2 (ILC2) can stimulate tumor growth by secreting pro-tumorigenic cytokines such as IL4, IL5 and IL13. However, the mechanisms by which type 2 immune cells traffic to the tumor microenvironment (TME) are unknown. Here, in pancreatic ductal adenocarcinoma (PDAC), we show that oncogenic KrasG12D (Kras*) increases the expression of IL33 in cancer cells, which upon secretion recruits and activates the TH2 and ILC2. Correspondingly, cancer cell-specific deletion of IL33 reduces TH2 and ILC2 recruitment and promotes tumor regression. Unexpectedly, we discovered that the cellular release of IL33 into the TME is dependent on the intratumoral fungal mycobiome. Genetic deletion of IL33 or anti-fungal treatment decreases TH2 and ILC2 infiltration and increases survival. Consistent with these murine data, high IL33 expression is observed in approximately 20% of human PDAC, and expression is mainly restricted to cancer cells. These data expand our knowledge of the mechanisms driving PDAC tumor progression and identifies therapeutically targetable pathways involving intratumoral mycobiome-driven secretion of IL33.
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Project description:We report the RNAseq of mouse pancreatic cancer cell lines with Kras ON vs Kras OFF. TH2 and innate lymphoid cells 2 (ILC2) can stimulate tumor growth by secreting pro-tumorigenic cytokines such as IL4, IL5 and IL13. However, the mechanisms by which type 2 immune cells traffic to the tumor microenvironment (TME) are unknown. Here, in pancreatic ductal adenocarcinoma (PDAC), we show that oncogenic KrasG12D (Kras*) increases the expression of IL33 in cancer cells, which upon secretion recruits and activates the TH2 and ILC2. Correspondingly, cancer cell-specific deletion of IL33 reduces TH2 and ILC2 recruitment and promotes tumor regression. Unexpectedly, we discovered that the cellular release of IL33 into the TME is dependent on the intratumoral fungal mycobiome. Genetic deletion of IL33 or anti-fungal treatment decreases TH2 and ILC2 infiltration and increases survival. Consistent with these murine data, high IL33 expression is observed in approximately 20% of human PDAC, and expression is mainly restricted to cancer cells. These data expand our knowledge of the mechanisms driving PDAC tumor progression and identifies therapeutically targetable pathways involving intratumoral mycobiome-driven secretion of IL33.
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Project description:Fungal mycobiome drives IL33 secretion and type 2 immunity in pancreatic cancer
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Project description:TH2 cells and innate lymphoid cells 2 (ILC2) can stimulate tumor growth by secreting pro-tumorigenic cytokines such as interleukin-4 (IL-4), IL-5, and IL-13. However, the mechanisms by which type 2 immune cells traffic to the tumor microenvironment are unknown. Here, we show that oncogenic KrasG12D increases IL-33 expression in pancreatic ductal adenocarcinoma (PDAC) cells, which recruits and activates TH2 and ILC2 cells. Correspondingly, cancer-cell-specific deletion of IL-33 reduces TH2 and ILC2 recruitment and promotes tumor regression. Unexpectedly, IL-33 secretion is dependent on the intratumoral fungal mycobiome. Genetic deletion of IL-33 or anti-fungal treatment decreases TH2 and ILC2 infiltration and increases survival. Consistently, high IL-33 expression is observed in approximately 20% of human PDAC, and expression is mainly restricted to cancer cells. These data expand our knowledge of the mechanisms driving PDAC tumor progression and identify therapeutically targetable pathways involving intratumoral mycobiome-driven secretion of IL-33.
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Project description:Fungal mycobiome drives IL33 secretion and type 2 immunity in pancreatic cancer
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