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肿瘤微环境中树突状细胞的代谢:用于免疫治疗。

Metabolism of Dendritic Cells in Tumor Microenvironment: For Immunotherapy.

机构信息

Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.

Department of Translational Medicine, Cancer Biological Treatment Center, Xiangya Hospital, Central South University, Changsha, China.

出版信息

Front Immunol. 2021 Feb 24;12:613492. doi: 10.3389/fimmu.2021.613492. eCollection 2021.

Abstract

Dendritic cells (DCs) are a type of an antigen-presenting cell which undertake a job on capturing antigens coming from pathogens or tumors and presenting to T cells for immune response. The metabolism of DCs controls its development, polarization, and maturation processes and provides energy support for its functions. However, the immune activity of DCs in tumor microenvironment (TME) is inhibited generally. Abnormal metabolism of tumor cells causes metabolic changes in TME, such as hyperglycolysis, lactate and lipid accumulation, acidification, tryptophan deprivation, which limit the function of DCs and lead to the occurrence of tumor immune escape. Combined metabolic regulation with immunotherapy can strengthen the ability of antigen-presentation and T cell activation of DCs, improve the existing anti-tumor therapy, and overcome the defects of DC-related therapies in the current stage, which has great potential in oncology therapy. Therefore, we reviewed the glucose, lipid, and amino acid metabolism of DCs, as well as the metabolic changes after being affected by TME. Together with the potential metabolic targets of DCs, possible anti-tumor therapeutic pathways were summarized.

摘要

树突状细胞(DCs)是一种抗原呈递细胞,其负责捕获来自病原体或肿瘤的抗原,并将其呈递给 T 细胞以引发免疫反应。DCs 的代谢控制着其发育、极化和成熟过程,并为其功能提供能量支持。然而,肿瘤微环境(TME)中的 DCs 的免疫活性通常受到抑制。肿瘤细胞的异常代谢导致 TME 中的代谢变化,如高糖酵解、乳酸和脂质积累、酸化、色氨酸耗竭,这些变化限制了 DCs 的功能,并导致肿瘤免疫逃逸的发生。联合代谢调控与免疫疗法可以增强 DCs 的抗原呈递和 T 细胞激活能力,改善现有的抗肿瘤治疗方法,并克服当前 DC 相关治疗的缺陷,在肿瘤治疗方面具有巨大的潜力。因此,我们综述了 DCs 的葡萄糖、脂质和氨基酸代谢,以及 TME 对其代谢的影响。同时,总结了 DCs 的潜在代谢靶点以及可能的抗肿瘤治疗途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76d/7959811/fd1a18facd51/fimmu-12-613492-g0001.jpg

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