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Researchers from the University of Geneva Uncover a Key Factor in Immunotherapy Effectiveness
Geneva, Switzerland – A groundbreaking study by scientists at the University of Geneva (UNIGE) has unveiled a crucial role played by a lymphatic-derived enzyme in boosting anti-tumor immunity. Published in Nature Communications, the research suggests that this enzyme could significantly improve the effectiveness of immunotherapies, providing new insights into cancer treatment.
The Role of Lymphatic Vessels in Tumor Development
Tumors form a structure around themselves known as the tumor stroma, which includes both blood and lymphatic vessels. These vessels facilitate essential biological exchanges, but lymphangiogenesis—the formation of new lymphatic vessels—is typically associated with poor prognosis due to its role in metastasis, the spread of cancer to other organs.
Despite this negative association, the latest research indicates that lymphatic vessels also play an essential role in immune response activation.
“While lymphatic vessels promote metastasis, they are also crucial for transporting immune cells and activating the anti-tumor immune response,” said Prof. Stéphanie Hugues, the study’s lead researcher from UNIGE’s Department of Pathology and Immunology and the Geneva Center for Inflammation Research.
A Newly Identified Enzyme Strengthens Immune Defense
The research team focused on the genetic expression of lymphatic endothelial cells in melanoma tumors and healthy mouse skin. They found an overexpression of an enzyme called Ch25h in the lymphatic endothelial cells of melanoma tumors, a result later confirmed in human samples. The more lymphatic vessels present in a melanoma, the higher the expression of this enzyme.
Patients with elevated levels of Ch25h exhibited better prognoses, especially those undergoing treatment with immune checkpoint inhibitors, a type of immunotherapy. Ch25h functions by converting cholesterol into 25-hydroxycholesterol, a metabolite known for its role in antiviral immunity. In the context of melanoma, it appears to help counteract the tumor’s immune-suppressing defenses, enhancing the effectiveness of immunotherapy.
A Potential Biomarker for Treatment Success
Further experiments revealed that eliminating Ch25h in mouse models led to a significant decrease in 25-hydroxycholesterol levels, resulting in suppressed immune activity and a weakened anti-tumor response. However, mice vaccinated with tumor antigens exhibited increased Ch25h expression, reinforcing immune cell activation and improving disease resistance.
This discovery suggests that Ch25h levels could serve as a biomarker to predict a patient’s response to immunotherapy, allowing for personalized treatment adjustments.
Rethinking Lymphangiogenesis in Cancer Therapy
Historically, lymphatic vessels were considered simple transport channels, but this study highlights their intricate role in immune modulation.
“Our work clearly shows that lymphatic endothelial cells are highly adaptable and respond dynamically to both tumor and immune system signals,” Prof. Hugues stated. “Rather than inhibiting lymphangiogenesis entirely, targeting specific functions of these cells could be a more effective strategy in cancer treatment.”
These findings pave the way for future research aimed at harnessing the power of lymphatic vessels to enhance immunotherapy outcomes, potentially revolutionizing how cancer treatments are administered.
Disclaimer:
This article summarizes scientific findings from a recent study and is intended for informational purposes only. It does not constitute medical advice. Patients should consult their healthcare providers before making any decisions regarding cancer treatment.
