IRF4 Promotes Immune Evasion and Shapes the Tumor Microenvironment in Follicular Lymphoma.

ABSTRACT: Twenty percent of patients with follicular lymphoma relapse early with poor outcomes; however, the molecular mechanisms underlying this aggressive behavior are unknown. Using a multiomic approach, we show that patients with follicular lymphoma with elevated IRF4 expression (IRF4hi) have increased transformation risk, dysregulated immune signaling, and a suppressive tumor microenvironment. Loss- and gain-of-function experiments in IRF4hi lymphoma cells, along with chromatin profiling, demonstrate that IRF4 impairs their interaction with T cells by repressing antigen presentation and co-receptor gene modules while promoting the expression of cytokines that antagonize T-follicular helper cell and regulatory T-cell functions. Additionally, IRF4 rewires tumor metabolism and restricts glucose av

SUBMITTER: Dasari S 

PROVIDER: S-EPMC12313276 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature