BATF2, also known as basic leucine zipper ATF-like transcription factor 2, is a transcription factor emerging as an important regulator in both the innate immune system and cancer-related processes. It is involved in various signaling pathways such as PTEN/AKT/β-catenin, PI3K-AKT, and is associated with interferon-activated immune response [1,3,4,6]. In the immune system, it impacts pro-inflammatory cytokine responses, and in cancer, it can act as a tumor suppressor [1,3,5,6,7]. Genetic models, especially KO mouse models, have been crucial in studying its functions.

In gastric cancer, BATF2 overexpression increased 5-Fu sensitivity, inhibited the ABCG2 drug transporter, and reduced the stem-like properties of cancer cells through the PTEN/AKT/β-catenin pathway, highlighting its role in regulating chemoresistance [1]. In glioblastoma multiforme, BATF2 inhibited glioma growth and myeloid-derived suppressor cells (MDSCs) recruitment. BATF2-overexpressing glioma cell-derived extracellular vesicles inhibited MDSCs chemotaxis, and the abundance of BATF2-positive extracellular vesicles in plasma could distinguish different stages of glioma [2]. In non-small cell lung cancer, BATF2 knockout mice studies showed that BATF2 inhibits programmed death-ligand 1 expression via the PI3K-AKT pathway and enhances CD8+ T-cell infiltration, suggesting its potential as a biomarker for immunotherapy efficacy [6].

In summary, BATF2 plays essential roles in the immune response and cancer development. Model-based research, particularly KO mouse models, has revealed its significance in diseases like gastric cancer, glioblastoma, and non-small cell lung cancer. It is involved in regulating chemoresistance, tumor growth, immune cell recruitment, and immune checkpoint molecule expression, providing insights for potential therapeutic strategies.