Core Viewpoint - The research highlights the potential of targeting necrotic lipid release in tumors to enhance immunosurveillance and improve cancer immunotherapy for glioblastoma, providing new therapeutic targets for this deadly brain tumor [2][5]. Group 1: Research Findings - The study utilized non-cancerous mouse embryonic stem cells to construct a genetically identical mouse teratoma model and identified genes affecting early cancer immune editing through whole-genome CRISPR screening [5]. - The deletion of pro-apoptotic tumor suppressor genes, including Trp53, exacerbated cell necrosis within teratomas, leading to the release of APOE lipid particles into the extracellular environment [5]. - Infiltrating T cells attracted to necrotic tumor regions accumulated lipids and became dysfunctional, but blocking T cell lipid uptake or inactivating mitochondrial permeability transition pore (mPTP) could reduce cell necrosis and restore immune surveillance [5]. Group 2: Implications for Human Cancer - The research further investigated the interaction between tumors and immunity in human glioblastoma (GBM), revealing that infiltrating T cells in TP53 mutant human GBM also exhibited APOE accumulation and dysfunction [5]. - The combination of anti-APOE antibodies with anti-PD-1 antibodies was found to synergistically enhance anti-tumor immune responses and prolong survival in mouse models [5]. Group 3: Mechanistic Insights - The study elucidated the association between mPTP-mediated tumor necrosis and immune evasion, indicating that inhibiting the uptake of lipids released from necrotic tumor cells by infiltrating immune cells can enhance the efficacy of cancer immunotherapy [5].