肿瘤细胞治疗研究
英文原题：A Multimodal Framework to Guide Solid Tumor Indications for Natural Killer Cell-Based Therapy.
这些发现提供了一个多模式框架，用于优先考虑肿瘤适应症并改进未来NK细胞临床试验的合理设计。
基于T细胞的免疫疗法在血液系统恶性肿瘤中取得了显著成功，但在实体瘤中仍然有限。自然杀伤（NK）细胞提供了一种有吸引力的互补方法，因为它们能够独立于新抗原呈递和MHC I类表达识别并杀伤肿瘤细胞。本研究整合了多组学分析、临床试验数据和转录组分析，以系统性地识别最有可能从基于NK细胞的疗法中获益的实体瘤适应症。免疫组织化学分析显示，NK细胞浸润多种肿瘤类型，在肾脏肿瘤中丰度最高。对177项临床试验的系统综述发现，不同实体瘤适应症的疗效存在差异，没有明显更优的肿瘤类型或干预措施。对超过10,000份TCGA样本的转录组分析评估了NK细胞浸润、细胞毒性适应性和肿瘤微环境组成，突出肾透明细胞癌、肺腺癌和鳞状细胞癌、宫颈和宫颈内膜癌以及间皮瘤作为未来临床评估的有前景候选者。总之，这些发现提供了一个多模式框架，用于优先考虑肿瘤适应症并改善未来NK细胞临床试验的合理设计。
T cell-based immunotherapies have achieved remarkable success in hematological malignancies but remain limited in solid tumors. Natural killer (NK) cells offer a compelling complementary approach, given their ability to recognize and kill tumor cells independently of neoantigen presentation and MHC class I expression. This study integrates multiomic analyses, clinical trial data, and transcriptomic analyses to systematically identify solid tumor indications most likely to benefit from NK cell-based therapies. Immunohistochemical analysis revealed that NK cells infiltrate multiple tumor types, with the highest abundance in kidney tumors. Systematic review of 177 clinical trials identified variable efficacy across solid tumor indications, without a clearly superior tumor type or intervention. Transcriptomic profiling of over 10,000 TCGA samples assessed NK cell infiltration, cytotoxic fitness, and tumor microenvironment composition, highlighting kidney renal cell carcinoma, lung adenocarcinoma and squamous cell carcinoma, cervical and endocervical cancers, and mesothelioma as promising candidates for future clinical evaluation. Together, these findings provide a multimodal framework to prioritize tumor indications and improve the rational design of future NK cell clinical trials.
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