Immunogenic cell death(ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system.However,effective type Ⅱ ICD inducers without biotoxicity are still very limited.Herein,a tentative drug-or photo sensitizer-free strategy was developed by employing enzymatic self-assembly of the peptide F-pY-T to induce mitochondrial oxidative stress in cancer cells.Upon dephosphorylation catalyzed by alkaline phosphatase overexpressed on cancer cells,the peptide F-pY-T self-assembled to form nanoparticles,which were subsequently internalized.These affected the morphology of mitochondria and induced serious reactive oxygen species production,causing the ICD characterized by the release of danger-associated molecular patterns(DAMPs).DAMPs enhanced specific immune responses by promoting the maturation of DCs and the intratumoral infiltration of tumor-specific T cells to eradicate tumor cells.The dramatic immunotherapeutic capacity could be enhanced further by combination therapy of F-pY-T and anti-PD-L1 agents without visible biotoxicity in the main organs.Thus,our results revealed an alternative strategy to induce efficient ICD by physically promoting mitochondrial oxidative stress.
目的:采用磁共振扩散张量成像(diffusion tensor imaging,DTI)技术,定量测量腰椎间盘相关腰骶丛神经根压迫症患者神经根各项异性分数(fractional anisotropy,FA)值,评估腰骶丛神经根DTI运用于腰椎间盘相关腰骶神经根压迫症术前诊断与预后评价的潜在价值。方法:对34例单侧腰骶丛神经根压迫症患者行腰骶神经根DTI检查,并行扩散张量示踪成像(diffusion tensor tractography,DTT),定量腰骶丛神经根3个层面神经根FA值,均使用日本骨科协会下腰痛评估治疗分数(Japanese Orthopedic Associationfor the Assessment of Treatment for Low Back Pain,JOA)进行临床功能症状评分,并进行相关性分析研究。结果:扩散张量示踪成像DTT显像所示,神经根神经纤维束异常均与临床症状相符,患侧神经根远中近段神经根FA值不相等,神经根FA值由近端至远端递减,患侧远中近段神经根FA值均低于健侧,病变责任神经根FA值与术前临床JOA评分值有较高的相关性。结论:腰骶丛神经根DTI成像可定性评价腰椎间盘相关腰骶神经根压迫症中责任神经根的损伤变性,并能通过神经根FA值,定量反映责任损伤神经根变性所致相应神经支配区域感觉异常及运动功能障碍。对于腰椎间盘相关腰骶神经根压迫症的术前诊断及预后评价具有较重要的临床应用价值。
