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Extracellular galectin 4 drives immune evasion and promotes T-cell apoptosis in pancreatic cancer

ABSTRACT: Extracellular galectin 4 drives immune evasion and promotes T-cell apoptosis in pancreatic cancer

PROVIDER: PRJNA890182 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21890623_1.fastq.gz	Fastqsanger.gz
	SRR21890623_2.fastq.gz	Fastqsanger.gz
	SRR21890624_1.fastq.gz	Fastqsanger.gz
	SRR21890624_2.fastq.gz	Fastqsanger.gz
	SRR21890576.fastq.gz	Fastqsanger.gz

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Extracellular galectin 4 drives immune evasion and promotes T-cell apoptosis in pancreatic cancer [RNA-Seq]

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Extracellular galectin 4 drives immune evasion and promotes T-cell apoptosis in pancreatic cancer [scRNA-Seq]

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Extracellular galectin 4 drives immune evasion and promotes T-cell apoptosis in pancreatic cancer [scRNA-Seq]

Project description:Pancreatic ductal adenocarcinoma (PDAC) is characterized by rich deposits of extracellular matrix (ECM), affecting the pathophysiology of the disease. Here, we identified galectin 4 (gal 4) as a cancer cell produced protein deposited into the ECM of PDAC tumors and detected high circulating levels of gal 4 in PDAC patients. In orthotopic transplantation experiments we observed increased infiltration of T-cells and prolonged survival in immunocompetent mice transplanted with cancer cells with reduced expression of gal 4. Increased survival was not observed in immunodeficient RAG1-/- mice, demonstrating that the effect was mediated by the adaptive immune system. Furthermore, by performing single-cell RNA-sequencing we found that the myeloid compartment and cancer-associated fibroblast (CAF) subtypes were altered in the transplanted tumors. Reduced gal 4 expression was associated with higher proportion of myofibroblastic CAFs and reduced numbers of inflammatory CAFs. We also found higher proportions of M1 macrophages, T-cells and antigen presenting dendritic cells in tumors with reduced gal 4 expression. Using a co-culture system, we observed that extracellular gal 4 induced apoptosis in T-cells by binding CD3, resulting in anergy or induction of apoptosis. Hence, we show that gal 4 is involved in immune evasion and identify gal 4 as a promising drug target for overcoming immunosuppression in PDAC.

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Extracellular galectin 4 drives immune evasion and promotes T-cell apoptosis in pancreatic cancer [RNA-Seq]

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Extracellular Galectin 4 Drives Immune Evasion and Promotes T-cell Apoptosis in Pancreatic Cancer.

Project description:Pancreatic ductal adenocarcinoma (PDAC) is characterized by rich deposits of extracellular matrix (ECM), affecting the pathophysiology of the disease. Here, we identified galectin 4 (gal 4) as a cancer cell-produced protein that was deposited into the ECM of PDAC tumors and detected high-circulating levels of gal 4 in patients with PDAC. In orthotopic transplantation experiments, we observed increased infiltration of T cells and prolonged survival in immunocompetent mice transplanted with cancer cells with reduced expression of gal 4. Increased survival was not observed in immunodeficient RAG1-/- mice, demonstrating that the effect was mediated by the adaptive immune system. By performing single-cell RNA-sequencing, we found that the myeloid compartment and cancer-associated fibroblast (CAF) subtypes were altered in the transplanted tumors. Reduced gal 4 expression associated with a higher proportion of myofibroblastic CAFs and reduced numbers of inflammatory CAFs. We also found higher proportions of M1 macrophages, T cells, and antigen-presenting dendritic cells in tumors with reduced gal 4 expression. Using a coculture system, we observed that extracellular gal 4 induced apoptosis in T cells by binding N-glycosylation residues on CD3ε/δ. Hence, we show that gal 4 is involved in immune evasion and identify gal 4 as a promising drug target for overcoming immunosuppression in PDAC.

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Extracellular galectin 4 drives immune evasion and promotes T-cell apoptosis in pancreatic cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

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A tumor specific super-enhancer drives immune evasion by guiding synchronous expression of PD-L1 and PD-L2

Project description:A tumor specific super-enhancer drives immune evasion by guiding synchronous expression of PD-L1 and PD-L2

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Galectin-3 regulates the expression of various genes in human gastric cancer cells

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Galectin-3 regulates the expression of various genes in human gastric cancer cells

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