Fig. 7
From: Cancer cells avoid ferroptosis induced by immune cells via fatty acid binding proteins
Mechanism of Fabp7-mediated ferroptosis resistance in PD1-Resistant tumors. In PD1-sensitive cancer cells, the interaction between PD1 on T cells and its ligand on cancer cells leads to the release of interferon gamma (IFNγ). This cytokine induces lipid peroxidation through polyunsaturated fatty acids (PUFAs), resulting in ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation. In contrast, PD1-resistant cancer cells exhibit enhanced survival mechanisms. These cells undergo epigenetic reprogramming facilitated by the upregulation of fatty acid binding protein 7 (Fabp7). Fabp7 alters lipid metabolism by modulating the activity of lysophosphatidylcholine acyltransferase 3 (Lpcat3), decreasing its histone acetylation. This process confers protection against ferroptosis. Additionally, PD1-resistant cells show an accumulation of apoptotic T cells caused by disruption of circadian clock genes expression, contributing to the overall resistance to immune-mediated cell death. Fabp7 also upregulates protective genes such as BMAL1 through epigenetic reprogramming, further enhancing resistance mechanisms. This illustration highlights the distinct molecular pathways by which Fabp7 mediates ferroptosis resistance and supports cancer cell survival, demonstrating its role in modulating lipid metabolism, mitochondrial function, and immune cell apoptosis to promote tumor resilience against PD1-mediated immunotherapy. Created with BioRender.com