Mechanism of PAX5 up-regulation in CD19+ tumor-associated macrophages

Determine the upstream molecular and cellular mechanisms that lead to high expression of the transcription factor PAX5 in CD19-positive tumor-associated macrophages within hepatocellular carcinoma, identifying the specific signaling pathways, environmental cues, or lineage programs responsible for inducing and sustaining PAX5 expression in these macrophages.

Background

PAX5 is a key transcription factor governing B-lineage commitment and CD19 expression, yet in this paper it is shown to be highly expressed in CD19+ tumor-associated macrophages (TAMs), where it drives enhanced oxidative phosphorylation, immunosuppressive protein accumulation (PD-L1 and CD73), and reduced phagocytosis.

Despite demonstrating PAX5’s central functional role in CD19+ TAMs, the authors explicitly note that the origin of elevated PAX5 expression in these macrophages is unknown, motivating investigation into the upstream regulators or microenvironmental factors that induce its expression.