Researchers have identified a key driver of angioimmunoblastic T cell lymphoma (AITL), an aggressive type of T cell cancer. Using a mouse model, they discovered a unique subset of tumor cells called Double-Expressor (DE) Tfh cells. These cells grow rapidly, boost B cell expansion, and show inflammatory signaling, making them central to tumor progression.
DE Tfh cells rely on EZH2, a gene regulator, for survival. When researchers deleted EZH2 in T cells, most tumors shrank completely, proving that these cells are essential for tumor maintenance. Tumors that persisted contained “escapee” DE Tfh cells that still had EZH2, confirming their critical role.
These findings point to potential treatments for AITL. Drugs like Tazemetostat, an FDA-approved EZH2 inhibitor, could target these DE Tfh cells, and experimental antibodies against CXCR6 also reduced tumors in mice. Human samples show that 20–30% of patients have similar DE Tfh cells, suggesting these therapies could help a meaningful subset of patients.