A Ludwig Cancer Research study found a key metabolic switch in T cells crucial for making memory T cells, which provide long-term immunity, and for a T cell subtype that helps fight tumors during immunotherapy.
The switch, PPARβ/δ, affects T cell memory and anti-cancer responses. Researchers suggest targeting this switch could boost cancer treatment effectiveness. When activated, Killer T cells use a special metabolism to fight cancer cells.
After clearing an infection, most killer T cells die. However, some become long-lasting central memory CD8+ T cells (Tcms) that can quickly fight the same pathogen if it returns. These Tcms switch off a specific metabolism to survive longer.
Researchers found that the protein PPARβ/δ helps in this process. Studies showed that PPARβ/δ is active in Tcms as the immune response winds down and is crucial for their survival and function. Without PPARβ/δ, Tcms and memory T cells in the intestines can’t persist effectively.
Researchers found that interleukin-15 and the protein TCF1 activate the PPARβ/δ pathway, which is crucial for forming and maintaining central memory T cells (Tcms). TCF1, also important for Tcm expansion, is present in a type of CD8+ T cells found in tumors. These cells can become exhausted or, with proper stimulation, become cancer-fighting T cells.
By targeting PPARβ/δ, they found that T cells could better fight tumors. Testing in mice showed that activating PPARβ/δ improved T cell effectiveness against melanoma. This suggests that targeting PPARβ/δ could enhance anti-tumor immunity.
The study concludes that targeting the PPARβ/δ pathway is crucial for maintaining immune memory and enhancing anti-tumor immunity. Activating this pathway improves the survival and function of central memory T cells and boosts their effectiveness in fighting tumors.
Journal reference :
- Alessio Bevilacqua, Fabien Franco et al., PPARβ/δ-orchestrated metabolic reprogramming supports the formation and maintenance of memory CD8+ T cells. Science Immunology. DOI: 10.1126/sciimmunol.adn2717.
