Prostaglandin D2 Axis Impairs Immunity Against Melanoma Via Dendritic Cells And Γδ T Cells In Middle-Aged Mice
As we age, our bodies undergo many changes, and unfortunately, the risk of developing cancers like melanoma increases. While current treatments, such as immune checkpoint blockade, have shown promise, many patients don’t respond or eventually develop resistance, highlighting the need for new approaches. Researchers have identified a crucial pathway that could be key to boosting our immune defenses against melanoma as we get older.
This new research focuses on a molecule called Prostaglandin D2 (PGD2) and its associated pathway, specifically involving an enzyme called Phospholipase A2 group IID (PLA2G2D) and a receptor known as PTGDR. It turns out that as we age, the activity of this pathway increases, and this heightened activity actually suppresses our immune system’s ability to combat melanoma. Think of it as a roadblock preventing our immune cells from effectively recognizing and destroying cancer cells.
In studies, when this PGD2 pathway was disrupted – either by removing the PLA2G2D enzyme or blocking the PTGDR receptor – there was a significant reduction in both the initial growth of melanoma tumors and their spread to other parts of the body. This protective effect was linked to a notable increase in the number and activity of a specialized type of immune cell called γδ T cells within the tumor. These γδ T cells are crucial defenders, and their enhanced presence means the immune system is better equipped to fight off the cancer.
The mechanism behind this improvement involves dendritic cells, which are important “presenters” that show foreign invaders to other immune cells. When the PTGDR receptor was absent on dendritic cells, these cells produced more of a molecule called IL-1β. This increased IL-1β then acted as a signal, further activating and drawing γδ T cells into the tumor site, creating a stronger anti-melanoma response.
These findings suggest that by targeting this specific PGD2 pathway, we might be able to “reprogram” aging dendritic cells. This reprogramming could empower our immune system to more effectively fight melanoma, offering a promising new therapeutic strategy, particularly for older adults where this pathway appears to be more active.
Source: link to paper