Harnessing the cDC1-NK Cross-Talk in the Tumor Microenvironment to Battle Cancer.
Harnessing the cDC1-NK Cross-Talk in the Tumor Microenvironment to Battle Cancer.
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DOI：
10.3389/fimmu.2020.631713
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发表时间：
2020
影响因子：
7.3
通讯作者：
Flórez-Grau G
中科院分区：
文献类型：
--
作者：
Bödder J;Zahan T;van Slooten R;Schreibelt G;de Vries IJM;Flórez-Grau G
免疫治疗方法已经彻底改变了癌症等多种疾病的治疗方法。肿瘤免疫治疗的主要目标是通过促进肿瘤细胞的识别和破坏来调节抗肿瘤免疫反应。近年来，人们对肿瘤微环境(TME)对免疫细胞的抑制作用有了更深入的了解，表明恢复TME的抑制作用是有效的免疫治疗的关键。自然杀伤(NK)细胞和树突状细胞(DC)是目前用于癌症患者的细胞类型。NK细胞之所以被使用，是因为它们能够通过细胞毒颗粒酶直接杀死肿瘤细胞。树突状细胞被用来增强抗肿瘤T细胞反应，其基础是呈递抗原和诱导肿瘤抗原特异性CD8+T细胞反应的能力。在临床前模型中，一个特殊的DC亚群，传统的1型DC(CDC1s)被证明是专门向CD8+T细胞交叉递送细胞外抗原的。这一特征使它们成为癌症治疗的一个很有前途的DC亚群。在TME中，cDC1s与NK细胞呈现双向串扰，导致cDc1募集、分化和成熟，以及NK细胞的激活和刺激。因此，TME中CDC1s和NK细胞的存在可能对免疫治疗的成功至关重要。在这篇综述中，我们讨论了CDC1s和NK细胞的功能，它们的双向相互作用以及可能改善肿瘤免疫治疗的策略。
Immunotherapeutic approaches have revolutionized the treatment of several diseases such as cancer. The main goal of immunotherapy for cancer is to modulate the anti-tumor immune responses by favoring the recognition and destruction of tumor cells. Recently, a better understanding of the suppressive effect of the tumor microenvironment (TME) on immune cells, indicates that restoring the suppressive effect of the TME is crucial for an efficient immunotherapy. Natural killer (NK) cells and dendritic cells (DCs) are cell types that are currently administered to cancer patients. NK cells are used because of their ability to kill tumor cells directly via cytotoxic granzymes. DCs are employed to enhance anti-tumor T cell responses based on their ability to present antigens and induce tumor-antigen specific CD8+ T cell responses. In preclinical models, a particular DC subset, conventional type 1 DCs (cDC1s) is shown to be specialized in cross-presenting extracellular antigens to CD8+ T cells. This feature makes them a promising DC subset for cancer treatment. Within the TME, cDC1s show a bidirectional cross-talk with NK cells, resulting in a higher cDC1 recruitment, differentiation, and maturation as well as activation and stimulation of NK cells. Consequently, the presence of cDC1s and NK cells within the TME might be of utmost importance for the success of immunotherapy. In this review, we discuss the function of cDC1s and NK cells, their bidirectional cross-talk and potential strategies that could improve cancer immunotherapy.