肿瘤细胞治疗研究
英文原题：Reprogramming Antitumor Immunity: NK Cell Strategies to Navigate the Immunosuppressive Tumor Microenvironment.
肿瘤免疫逃逸是持久癌症免疫治疗的主要障碍，因为晚期恶性肿瘤会形成一种肿瘤微环境（TME），该微环境优先使T细胞应答耗竭和失能。
肿瘤免疫逃逸是持久癌症免疫治疗的主要障碍，因为晚期恶性肿瘤会形成一种肿瘤微环境（TME），该微环境优先使T细胞应答耗竭并失能。尽管大多数已获批的细胞疗法基于T细胞，但这一局限性促使人们探索替代的效应细胞平台。自然杀伤（NK）细胞是能够不依赖抗原识别和杀伤的先天性细胞毒性淋巴细胞，为具有更佳安全性的下一代疗法提供了有吸引力的基础。在本综述中，我们首先概述限制细胞毒性淋巴细胞功能的免疫抑制性TME的细胞、分子和代谢特征，重点阐述限制免疫细胞介导应答的机制。然后，我们总结能够绕过这些屏障的NK细胞生物学的关键方面，并批判性评估当前基于NK的策略，包括工程化嵌合抗原受体（CAR）-NK产品以及代谢和迁移干预。最后，我们强调用于CAR-NK生成的新兴体内病毒和mRNA/脂质纳米颗粒平台，以及它们在提高可扩展性和治疗持久性方面的潜力。
Tumor immune escape is a major barrier to durable cancer immunotherapy, as advanced malignancies create a tumor microenvironment (TME) that preferentially exhausts and disables T cell responses. While most approved cell therapies are T cell-based, this limitation motivates the exploration of an alternative effector cell platform. Natural killer (NK) cells, innate cytotoxic lymphocytes capable of antigen-independent recognition and killing, offer a compelling foundation for next-generation therapies with an improved safety profile. In this review, we first outline the cellular, molecular, and metabolic features of the immunosuppressive TME that restrict cytotoxic lymphocyte function, emphasizing mechanisms that limit immune cell-mediated responses. We then summarize key aspects of NK cell biology that can circumvent these barriers and critically evaluate current NK-based strategies, including engineered chimeric antigen receptor (CAR)-NK products and metabolic and trafficking interventions. Finally, we highlight emerging in vivo viral and mRNA/lipid nanoparticle platforms for CAR-NK generation and their potential to enhance scalability and therapeutic durability.
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