Tumor-associated neutrophils upregulate Nectin2 expression, creating the immunosuppressive microenvironment in pancreatic ductal adenocarcinoma
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Tumor-associated neutrophils (TANs) promote pancreatic cancer by secreting CCL5 and upregulating Nectin2. Targeting Nectin2 offers a new immunotherapy strategy for pancreatic ductal adenocarcinoma (PDAC).
Area Of Science
- Immunology
- Oncology
- Cancer Research
Background
- Tumor-associated neutrophils (TANs) are key players in pancreatic ductal adenocarcinoma (PDAC) progression.
- Understanding TANs' pro-tumor mechanisms is crucial for developing effective PDAC immunotherapies.
Purpose Of The Study
- To elucidate the pro-tumor mechanisms of TANs in PDAC.
- To identify novel therapeutic targets for PDAC immunotherapy.
Main Methods
- Utilized microarray, cytokine array, and single-cell transcriptomics.
- Employed in vitro co-culture and in vivo models using human and mouse TANs.
- Analyzed TAN interactions with cancer cells and T-cells.
Main Results
- Increased TAN infiltration correlates with poor PDAC patient survival.
- TANs secrete CCL5, promoting cancer cell migration and invasion.
- TANs upregulate Nectin2, leading to CD8+ T-cell exhaustion; blocking Nectin2 improves T-cell function and suppresses tumor growth.
Conclusions
- TANs drive PDAC progression via CCL5 secretion and Nectin2 upregulation.
- Targeting the immune checkpoint Nectin2 presents a novel immunotherapy strategy for PDAC.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...