Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, Centre for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
NCI CCR Liver Cancer Program, National Institutes of Health, Bethesda, MD, USA.
Nat Rev Cancer. 2023 Jun;23(6):351-371. doi: 10.1038/s41568-023-00562-w. Epub 2023 Apr 20.
Immunotherapies targeting conventional T cells have revolutionized systemic treatment for many cancers, yet only a subset of patients benefit from these approaches. A better understanding of the complex immune microenvironment of tumours is needed to design the next generation of immunotherapeutics. Innate lymphoid cells (ILCs) and innate-like T cells (ILTCs) are abundant, tissue-resident lymphocytes that have recently been shown to have critical roles in many types of cancers. ILCs and ILTCs rapidly respond to changes in their surrounding environment and act as the first responders to bridge innate and adaptive immunity. This places ILCs and ILTCs as pivotal orchestrators of the final antitumour immune response. In this Review, we outline hallmarks of ILCs and ILTCs and discuss their emerging role in antitumour immunity, as well as the pathophysiological adaptations leading to their pro-tumorigenic function. We explore the pleiotropic, in parts redundant and sometimes opposing, mechanisms that underlie the delicate interplay between the different subsets of ILCs and ILTCs. Finally, we highlight their role in amplifying and complementing conventional T cell functions and summarize immunotherapeutic strategies for targeting ILCs and ILTCs in cancer.
靶向常规 T 细胞的免疫疗法已经彻底改变了许多癌症的系统治疗方法,但只有一部分患者从中受益。为了设计下一代免疫疗法,我们需要更好地了解肿瘤复杂的免疫微环境。先天淋巴细胞(ILC)和先天样 T 细胞(ILTC)是丰富的组织驻留淋巴细胞,最近它们在许多类型的癌症中发挥着关键作用。ILC 和 ILTC 可以迅速响应周围环境的变化,并充当先天免疫和适应性免疫之间的桥梁,成为第一道反应者。这使得 ILC 和 ILTC 成为抗肿瘤免疫反应的关键协调者。在这篇综述中,我们概述了 ILC 和 ILTC 的特征,并讨论了它们在抗肿瘤免疫中的新兴作用,以及导致其促进肿瘤发生功能的病理生理适应性。我们探讨了不同 ILC 和 ILTC 亚群之间微妙相互作用所基于的多效性、部分冗余且有时相互矛盾的机制。最后,我们强调了它们在放大和补充常规 T 细胞功能方面的作用,并总结了针对癌症中 ILC 和 ILTC 的免疫治疗策略。
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