通过靶向肿瘤相关巨噬细胞的嵌合受体工程化溶瘤病毒重振内源性抗肿瘤免疫
Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor response assessment on imaging following immunotherapy.
Tumor response assessment on imaging following immunotherapy.
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近年来,针对癌症治疗开发了多种系统性免疫疗法,例如针对免疫检查点的单克隆抗体(mABs)(免疫检查点抑制剂,ICIs)、溶瘤病毒、细胞因子、癌症疫苗以及过继性细胞转移。据估计,ICIs 适用于 38.5% 的转移性实体瘤或血液肿瘤患者,尤其在多种肿瘤疾病中(如黑色素瘤、肺癌、膀胱癌、肾癌、头颈癌)表现出持久的疾病控制和总生存期获益。由于其基于 T 细胞激活的独特作用机制,免疫治疗的应答具有不同的模式,如治疗应答前的进展(假性进展)、超进展以及治疗后的分离应答。由于这些特征在实体瘤疗效评价标准 1.1 版(RECIST 1.1)——肿瘤学中疗效评估的标准——中并未涉及,因此为免疫治疗定义了新的标准。这些新的形态学标准中最重要的变化是:首先,在出现进展时需要进行确认性影像学检查;其次,新病灶的出现不一定被视为疾病进展。
迄今为止,已开发了五种形态学标准(免疫相关应答标准(irRC)、免疫相关 RECIST(irRECIST)、免疫 RECIST(iRECIST)、免疫改良 RECIST(imRECIST)和瘤内 RECIST(itRECIST)),以准确评估靶病灶大小的变化,并考虑到免疫治疗后特定的应答模式。除形态学缓解标准外,2-脱氧-2-[18F]氟-D-葡萄糖正电子发射断层扫描/计算机断层扫描(18F-FDG-PET/CT)是代谢缓解评估的一种有前景的选择,目前使用四种代谢标准(免疫检查点抑制剂治疗早期缓解预测PET/CT标准(PECRIT)、免疫治疗PET缓解评估标准(PERCIMT)、免疫治疗改良实体瘤PET缓解标准(imPERCIST5)和免疫PERCIST(iPERCIST))。
此外,有证据表明18F-FDG-PET/CT上的参数,如标准化摄取值(SUV)max以及若干放射性示踪剂,例如针对PD-L1的示踪剂,可能是缓解的潜在影像生物标志物。而且,人瘤内免疫治疗(HIT-IT)的出现,其特征是将免疫刺激剂直接注射到肿瘤病灶中,使影像评估具有了新的重要性。本文综述了免疫治疗后肿瘤缓解和进展的特定影像模式以及可用的影像缓解标准。
In recent years, various systemic immunotherapies have been developed for cancer treatment, such as monoclonal antibodies (mABs) directed against immune checkpoints (immune checkpoint inhibitors, ICIs), oncolytic viruses, cytokines, cancer vaccines, and adoptive cell transfer. While being estimated to be eligible in 38. 5% of patients with metastatic solid or hematological tumors, ICIs, in particular, demonstrate durable disease control across many oncologic diseases (e. g. , in melanoma, lung, bladder, renal, head, and neck cancers) and overall survival benefits. Due to their unique mechanisms of action based on T-cell activation, response to immunotherapies is characterized by different patterns, such as progression prior to treatment response (pseudoprogression), hyperprogression, and dissociated responses following treatment.
Because these features are not encountered in the Response Evaluation Criteria in Solid Tumors version 1. 1 (RECIST 1. 1), which is the standard for response assessment in oncology, new criteria were defined for immunotherapies. The most important changes in these new morphologic criteria are, firstly, the requirement for confirmatory imaging examinations in case of progression, and secondly, the appearance of new lesions is not necessarily considered a progressive disease.
Until today, five morphologic (immune-related response criteria (irRC), immune-related RECIST (irRECIST), immune RECIST (iRECIST), immune-modified RECIST (imRECIST), and intra-tumoral RECIST (itRECIST)) criteria have been developed to accurately assess changes in target lesion sizes, taking into account the specific response patterns after immunotherapy.
In addition to morphologic response criteria, 2-deoxy-2-[ 18 F]fluoro-D-glucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) is a promising option for metabolic response assessment and four metabolic criteria are used (PET/CT Criteria for Early Prediction of Response to Immune Checkpoint Inhibitor Therapy (PECRIT), PET Response Evaluation Criteria for Immunotherapy (PERCIMT), immunotherapy-modified PET Response Criteria in Solid Tumors (imPERCIST5), and immune PERCIST (iPERCIST)).
Besides, there is evidence that parameters on 18 F-FDG-PET/CT, such as the standardized uptake value (SUV)max and several radiotracers, e. g. , directed against PD-L1, may be potential imaging biomarkers of response.
Moreover, the emerge of human intratumoral immunotherapy (HIT-IT), characterized by the direct injection of immunostimulatory agents into a tumor lesion, has given new importance to imaging assessment. This article reviews the specific imaging patterns of tumor response and progression and available imaging response criteria following immunotherapy.
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