NK and NKT cells have distinct properties and functions in cancer
NK and NKT cells have distinct properties and functions in cancer
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DOI：
10.1038/s41388-021-01880-9
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发表时间：
2021-06-12
期刊：
影响因子：
8
通讯作者：
Peng, Guangyong
中科院分区：
文献类型：
--
作者：
Liu, Xia;Li, Lingyun;Peng, Guangyong
自然杀伤细胞（NK）和自然杀伤T细胞（NKT）是先天免疫系统中两个重要的细胞亚群。NK和NKT细胞在抗肿瘤免疫中具有许多共同的表型和功能；然而，在肿瘤发生和发展过程中，肿瘤微环境中表型和功能相互作用的动态变化是未知的。在这里，我们报道NK和NKT细胞在肿瘤发展过程中具有不同的特性、代谢谱和功能。通过小鼠E0771乳腺癌和B16黑色素瘤模型，我们发现NK细胞和NKT细胞都动态参与了对癌症的免疫反应，但在肿瘤发生和进展过程中，NK细胞和NKT细胞在肿瘤部位和其他外周器官中的分布和表型特征不同。在肿瘤发展的早期阶段，NK和NKT细胞都表现出效应特性。在癌症晚期，NK和NKT细胞的细胞毒性受损，功能失调。NK细胞变成衰老细胞，而NKT细胞，除了不变的NKT （iNKT）细胞，在晚期癌症中耗尽。相反，iNKT细胞在乳房肿瘤微环境中的激活和效应功能增加。此外，衰老的NK细胞糖脂代谢增高，但衰竭的NKT细胞在乳腺癌和黑色素瘤肿瘤模型的肿瘤微环境中均表现出代谢不平衡。这些研究提供了对NK和NKT细胞在抗肿瘤免疫中的动态和独特功能作用的更好理解，这可能有助于开发针对NK和NKT细胞的新型免疫疗法来治疗癌症。
Natural killer (NK) and natural killer T (NKT) cells are two important cell subsets of the innate immune system. NK and NKT cells share many phenotypes and functions for anti-tumor immunity; however, the dynamic changes in phenotypes and functional interactions within the tumor microenvironment during tumor development and progression are unknown. Here we report that NK and NKT cells have distinct properties, metabolic profiles, and functions during tumor development. Using the mouse E0771 breast cancer and B16 melanoma models, we found that both NK and NKT cells are dynamically involved in the immune responses to cancer but have distinct distributions and phenotypic profiles in tumor sites and other peripheral organs during the course of tumor development and progression. In the early stages of tumor development, both NK and NKT cells exhibit effector properties. In the later cancer stages, NK and NKT cells have impaired cytotoxic capacities and dysfunctional states. NK cells become senescent cells, while NKT cells, other than invariant NKT (iNKT) cells, are exhausted in the advanced cancers. In contrast, iNKT cells develop increases in activation and effector function within the breast tumor microenvironment. In addition, senescent NK cells have heightened glucose and lipid metabolism, but exhausted NKT cells display unbalanced metabolism in tumor microenvironments of both breast cancer and melanoma tumor models. These studies provide a better understanding of the dynamic and distinct functional roles of NK and NKT cells in anti-tumor immunity, which may facilitate the development of novel immunotherapies targeting NK and NKT cells for cancer treatment.