Yin Peng, Cao Pei, Liang Yu, Wang Chao, Tian Yu
International Genome Center, Jiangsu University, Zhenjiang 212013, China; School of Medicine, Jiangsu University, Zhenjiang 212013, China.
Northern Jiangsu Cardiovascular Disease Prevention and Treatment Research Institute, Jiangsu University, Yan Cheng 224000, China; Yancheng Third People's Hospital, 224000, China; School of Life Sciences, Jiangsu University, Zhenjiang 212013, China; International Genome Center, Jiangsu University, Zhenjiang 212013, China.
Biochim Biophys Acta Rev Cancer. 2025 Oct;1880(5):189430. doi: 10.1016/j.bbcan.2025.189430. Epub 2025 Aug 26.
Innate lymphoid cells (ILCs) are emerging as powerful players in the immune system, capable of dramatically influencing tumor immunity. Their extraordinary plasticity, which allows them to adapt to dynamic changes in the tumor microenvironment, positions them as a double-edged sword in cancer immunotherapy. While they can drive anti-tumor immune responses, they can also promote tumor progression under certain conditions. In this review, we delve into the multifaceted roles of ILCs-focusing on ILC1, ILC2, and ILC3-and explore how their functional plasticity can be harnessed to shift their activities from immune suppression to potent anti-tumor actions. We highlight groundbreaking therapeutic strategies aimed at modulating ILC plasticity, such as metabolic reprogramming, cytokine therapy, and CAR-ILC1 therapy, each designed to enhance the anti-tumor potential of these cells. Despite the immense promise, challenges remain, including immune suppression within the TME and the short-lived efficacy of cytokines. However, targeting ILC plasticity offers a transformative approach to overcome these hurdles, presenting an opportunity to personalize cancer treatment and create tailored immunotherapies that dynamically modulate the immune response. This review underscores the game-changing potential of ILC-based therapies and provides insights into the next generation of cancer immunotherapies that could revolutionize the fight against cancer.
固有淋巴细胞（ILCs）正在成为免疫系统中的强大参与者，能够显著影响肿瘤免疫。它们具有非凡的可塑性，使其能够适应肿瘤微环境中的动态变化，这使它们在癌症免疫治疗中成为一把双刃剑。虽然它们可以驱动抗肿瘤免疫反应，但在某些情况下也会促进肿瘤进展。在这篇综述中，我们深入探讨ILCs的多方面作用——重点关注ILC1、ILC2和ILC3——并探索如何利用它们的功能可塑性将其活动从免疫抑制转变为强大的抗肿瘤作用。我们强调了旨在调节ILC可塑性的开创性治疗策略，如代谢重编程、细胞因子疗法和CAR-ILC1疗法，每种策略都旨在增强这些细胞的抗肿瘤潜力。尽管前景广阔，但挑战依然存在，包括肿瘤微环境中的免疫抑制和细胞因子的短期疗效。然而，针对ILC可塑性提供了一种变革性方法来克服这些障碍，为个性化癌症治疗和创建动态调节免疫反应的定制免疫疗法提供了机会。这篇综述强调了基于ILC的疗法的变革潜力，并为可能彻底改变抗癌斗争的下一代癌症免疫疗法提供了见解。
