CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
我们的工作确立了CD81作为连接放射抵抗与免疫逃逸的关键桥梁,其通过维持GBM中CD274的丰度发挥作用,并突显CD81作为优化放射免疫治疗的有前景的治疗靶点。
英文原题:Cardiovascular Complications of Immune Effector Cell Therapies in Pediatric Hematological and Solid Tumors.
在接受 IEC 治疗的患者中,少数出现了显著的血流动力学障碍。所有发生心功能障碍的患者其功能均恢复,且无心血管相关死亡。
免疫效应细胞(IEC)疗法,包括嵌合抗原受体(CAR)修饰的T细胞疗法,已在儿童B细胞急性淋巴细胞白血病(B-ALL)中显示出疗效,并正在其他恶性肿瘤中进行研究。与IEC疗法相关的常见毒性是细胞因子释放综合征(CRS),其可因全身性炎症导致心血管失代偿。关于儿童心血管不良影响的数据有限。本研究旨在描述IEC疗法在患有血液系统和实体肿瘤恶性肿瘤的儿科患者中的心血管不良影响特征。
我们回顾性审查了2014年1月至2023年6月在德克萨斯儿童医院接受针对血液、实体和脑肿瘤恶性肿瘤中不同靶点的IECs治疗的患者。主要终点是输注后30天内需要血管活性药物支持的低血压和/或心力衰竭。
共203例患者符合纳入标准。142例(70%)儿童患者有治疗前超声心动图,其中140例(96%)基线收缩功能正常。26例(13%)患者出现需要血管活性药物支持的低血压。血液系统恶性肿瘤适应证(p = 0.002)、全身照射(TBI)(p = 0.002)和异基因造血干细胞移植(HCT)(p = 0.035)与需要血管活性药物支持的低血压风险增加相关。14例达到主要终点的患者有随访超声心动图,所有患者均显示6个月内恢复至基线。
BACKGROUND: Immune effector cell (IEC) therapies, including chimeric antigen receptor (CAR)-modified T-cell therapy, have shown efficacy in pediatric B-cell acute lymphoblastic leukemia (B-ALL) and are being investigated for other malignancies. A common toxicity associated with IEC therapy is cytokine release syndrome (CRS), which can lead to cardiovascular decompensation due to systemic inflammation. Data are limited regarding cardiovascular adverse effects in children. This study aims to describe the cardiovascular adverse effect profile of IEC therapies in pediatric patients with hematologic and solid tumor malignancies. METHODS: We retrospectively reviewed patients who received IECs directed towards various targets in patients with hematologic, solid, and brain tumor malignancies from January 2014 to June 2023 at Texas Children's Hospital. The primary end point was hypotension requiring vasoactive support and/or heart failure within 30 days of infusion. RESULTS: A total of 203 patients met inclusion criteria. Pretreatment echocardiogram was available for 142 (70%) pediatric patients, of whom 140 (96%) had normal baseline systolic function. Hypotension requiring vasoactive support occurred in 26 (13%) patients. Hematologic malignancy indications (p = 0.002), total body irradiation (TBI) (p = 0.002), and allogenic hematopoietic stem cell transplants (HCT) (p = 0.035) were associated with increased risk of hypotension requiring vasoactive support. Follow-up echocardiograms were available for 14 patients who met the primary end point, and all showed return to baseline within 6 months. CONCLUSIONS: Significant hemodynamic compromise occurred in a minority of patients treated with IEC therapies. All experiencing cardiac dysfunction had recovery of function, and there was no cardiovascular-related mortality.
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