决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:AI-driven radiomics and radiogenomics: supporting the assessment and differentiation of pseudoprogression in cellular immunotherapy for glioblastoma.
胶质母细胞瘤(GBM)是成人中最具侵袭性的原发性脑肿瘤,治疗后也难以判断一个人的健康状况是否有所改善。
胶质母细胞瘤(GBM)是成人中最具侵袭性的原发性脑肿瘤,治疗后也难以判断患者的健康状况是否改善。假性进展(PsP),尤其是在放疗以及替莫唑胺联合新型免疫治疗之后,可能被常规MRI误判为真性进展(TP),从而导致过早终止治疗或不必要地强化治疗。尽管RANO、iRANO和RANO 2.0改进了疗效评估,但单纯结构MRI无法揭示肿瘤微环境的生物学复杂性。基于人工智能(AI)的影像组学和影像基因组学有助于刻画GBM的特征。多种磁共振成像(MRI)序列用于获取定量数据,如常规T1加权图像、弥散加权图像、灌注加权图像等,以获取细胞密度、血管分布、免疫细胞浓度、分子改变及治疗效应等信息。将影像特征与液体活检、基因组数据和患者健康记录相结合,可提高诊断准确性,并发现用于免疫检查点抑制剂和CAR-T细胞治疗临床试验的高灵敏度替代标志物。临床转化仍面临诸多局限,如研究方案不一致、研究队列较小、外部验证不足、模型可解释性不够以及参考标准不一致。未来,许多研究团队将开展多中心验证、标准化工作流程、开源报告并发布具有临床可解释性的模型。上述方法可减少PsP引起的偏倚,改善假性进展与真性进展的鉴别,从而促进大多数患者及时接受治疗。
Glioblastoma (GBM) is the most aggressive type of primary brain tumour in adults, and after treatment, it is also difficult to know whether a person's health has improved. Pseudoprogression (PsP), particularly following radiotherapy and combination therapy with temozolomide and new immunotherapies, may be falsely identified as true progression (TP) by conventional MRI, thus leading to premature termination of treatment or unnecessary intensification of therapy. Although RANO, iRANO and RANO 2.0 have improved the assessment of response, structural MRI alone is unable to reveal the biological complexity of the tumour microenvironment. Artificial Intelligence (AI)-based radiomics and radiogenomics aid in the characterisation of GBM. Several Magnetic Resonance Imaging (MRI) sequences are used to obtain quantitative data, such as the conventional T1-weighted images, diffusion-weighted images, perfusion-weighted images and others, to acquire information on cell density, blood vessel distribution, immune cell concentration, molecular modifications and the effect of therapy. Combine imaging characteristics with liquid biopsy, genomic data and patient health records to enhance the accuracy of diagnosis and discover high-sensitivity surrogate markers for immune checkpoint inhibitor and CAR-T cell therapy clinical trials. Clinical translation still faces numerous limitations such as inconsistent research protocols, small study cohorts, insufficient external validation, inadequate model interpretability and inconsistent reference standards. In the future, many research groups will conduct multi-centre validation, standardize workflows, open-source reporting and release clinically interpretable models. The above ways can reduce the bias induced by PsP and improve differentiation between pseudoprogression and true progression to facilitate prompt treatment for most people.
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