In new research published in Nature Cancer, a team led by Professor Michael Schmid from the University of Liverpool has uncovered new insights into how pancreatic cancer spreads to the liver, a common and deadly progression of pancreatic ductal adenocarcinoma (PDAC).
This discovery opens up potential new avenues for treating this aggressive cancer, particularly in its metastatic stage.
Pancreatic cancer, notorious for its poor prognosis and aggressive nature, often metastasizes to the liver in 40–50% of cases. Until now, effective therapies to combat liver metastasis in pancreatic cancer patients have been notably absent.
Schmid’s team’s research focuses on the role of efferocytosis—the process of clearing dead cells—during the early stages of liver metastasis.
Their findings reveal that this process significantly contributes to creating an immunosuppressive environment that allows cancer cells to thrive undetected by the body’s immune system.
The study identifies that within the liver, the presence of metastasis-associated macrophages—immune cells known for their role in tumor growth—becomes notably immunosuppressive.
These macrophages are reprogrammed through the efferocytosis of dead cells, leading to diminished T cell activation and, consequently, an increased tumor burden.
By blocking the efferocytosis pathway, the researchers successfully restored T cell activity and reduced the metastatic tumor load.
Dr. Yuliana Astuti, the study’s first author, emphasizes the diverse nature of macrophages in pancreatic cancer liver metastases.
The team’s use of single-cell technologies unveiled a dynamic range of macrophage functions, from stimulating to suppressing the immune response.
The study highlights the critical role of dead cell engulfment in steering macrophages towards an immunosuppressive behavior, suggesting that targeted intervention in this process could significantly enhance tumor immunity and curb PDAC metastasis.
Professor Ainhoa Mielgo, a key contributor to the study, points out the urgent need for effective treatments for pancreatic cancer, especially when it spreads to the liver.
The findings of this research are seen as a hopeful stride toward identifying actionable mechanisms that could prevent the growth and spread of pancreatic cancer cells in the liver.
The team’s work not only sheds light on the intricate mechanisms of cancer metastasis but also charts a course for future therapeutic strategies aimed at targeting specific aspects of the tumor microenvironment for the benefit of patients battling metastatic pancreatic cancer.
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The research findings can be found in Nature Cancer.
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