The Tumor Microenvironment-A Metabolic Obstacle to NK Cells' Activity.
The Tumor Microenvironment-A Metabolic Obstacle to NK Cells' Activity.
复制标题
肿瘤微环境-NK细胞活性的代谢障碍
DOI：
10.3390/cancers12123542
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发表时间：
2020-11-27
期刊：
影响因子：
5.2
通讯作者：
Winiarska M
中科院分区：
文献类型：
--
作者：
Domagala J;Lachota M;Klopotowska M;Graczyk-Jarzynka A;Domagala A;Zhylko A;Soroczynska K;Winiarska M
自然杀伤细胞能够有效地消除肿瘤细胞而无需预先致敏，因此最近对其在肿瘤免疫治疗中的应用的兴趣增加。然而，肿瘤细胞与肿瘤相关细胞协同作用以产生特异性免疫抑制小生境，这限制了NK细胞的活性。在这篇综述中，我们提供了负责NK细胞的细胞毒性机制的分子机制的详细描述。此外，我们简要描述了肿瘤微环境，并总结了肿瘤生态位内的各种代谢因子如何调节NK细胞的抗肿瘤能力。此外，我们还讨论了增强NK细胞功能的新型抗肿瘤治疗的潜在策略和意义。NK细胞具有识别和破坏肿瘤细胞的独特能力，而不需要宿主的预先免疫。保持对健康细胞的耐受性使它们成为几乎所有类型癌症的有吸引力的治疗工具。不幸的是，与恶性转化和肿瘤进展相关的代谢变化导致肿瘤微环境内的免疫抑制，这反过来限制了各种免疫疗法的功效。在这篇综述中，我们简要介绍了肿瘤微环境的代谢变化特征。肿瘤和肿瘤相关细胞都产生和分泌直接或间接阻止NK细胞细胞毒性的因子。在这里，我们描绘了负责代谢因子抑制免疫效应细胞的分子机制。最后，我们总结了增强NK细胞功能治疗肿瘤的策略。
Natural killer cells are able to effectively eliminate tumor cells without previous sensitization, therefore the interest in their application in tumor immunotherapy has recently increased. However, tumor cells synergize with tumor-associated cells to create a specific immunosuppressive niche, which limits the activity of NK cells. In this review, we provide a detailed description of molecular mechanisms responsible for NK cells’ cytotoxic machinery. Moreover, we shortly characterize the tumor microenvironment and summarize how various metabolic factors within the tumor niche modulate antitumor capacity of NK cells. Moreover, we discuss the potential strategies and implications for the novel antitumor therapies augmenting NK cells functions. NK cells have unique capabilities of recognition and destruction of tumor cells, without the requirement for prior immunization of the host. Maintaining tolerance to healthy cells makes them an attractive therapeutic tool for almost all types of cancer. Unfortunately, metabolic changes associated with malignant transformation and tumor progression lead to immunosuppression within the tumor microenvironment, which in turn limits the efficacy of various immunotherapies. In this review, we provide a brief description of the metabolic changes characteristic for the tumor microenvironment. Both tumor and tumor-associated cells produce and secrete factors that directly or indirectly prevent NK cell cytotoxicity. Here, we depict the molecular mechanisms responsible for the inhibition of immune effector cells by metabolic factors. Finally, we summarize the strategies to enhance NK cell function for the treatment of tumors.
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DOI：
10.1084/jem.176.2.327
发表时间：
1992-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Baixeras E;Huard B;Miossec C;Jitsukawa S;Martin M;Hercend T;Auffray C;Triebel F;Piatier-Tonneau D
通讯作者：
Piatier-Tonneau D
影响因子：
10.1
作者：
Aydin, Ebru;Johansson, Junko;Martner, Anna
通讯作者：
Martner, Anna
影响因子：
8.7
作者：
Allard B;Longhi MS;Robson SC;Stagg J
通讯作者：
Stagg J
影响因子：
5.6
作者：
Beldi-Ferchiou A;Caillat-Zucman S
通讯作者：
Caillat-Zucman S
影响因子：
20.3
作者：
Ahn, Yong-Oon;Blazar, Bruce R.;Verneris, Michael R.
通讯作者：
Verneris, Michael R.