Strategies to overcome DC dysregulation in the tumor microenvironment.
Strategies to overcome DC dysregulation in the tumor microenvironment.
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DOI：
10.3389/fimmu.2022.980709
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发表时间：
2022
影响因子：
7.3
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中科院分区：
文献类型：
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在肿瘤微环境(TME)中，树突状细胞(DC)在调节抗癌免疫中起着关键作用。它们通过处理肿瘤抗原并将其呈递给T细胞，从而启动抗肿瘤反应，从而与获得性免疫联系在一起。然而，树突状细胞亚群也能诱导免疫耐受，导致肿瘤免疫逃逸。在这方面，TME在对DC功能产生不利影响方面发挥了重要作用。更好地了解TME中的DC损伤机制将导致更有效的DC靶向免疫治疗。在此，我们综述了TME中DC的不同亚型和功能，包括常规DC、浆细胞样DC和新提出的亚群mregDC。我们进一步关注癌细胞如何调节树突状细胞逃避宿主的免疫监视。免疫检查点的表达、小分子介质、代谢产物、肿瘤前免疫原性的丧失以及肿瘤和肿瘤吸引的免疫抑制细胞分泌的促肿瘤细胞因子抑制DC的分化和功能。最后，我们讨论了现有治疗方法对DC的影响，如免疫检查点阻断。将强调创造性的DC靶向治疗策略，包括癌症疫苗和基于细胞的治疗。
Dendritic cells (DCs) play a key role to modulate anti-cancer immunity in the tumor microenvironment (TME). They link innate to adaptive immunity by processing and presenting tumor antigens to T cells thereby initiating an anti-tumor response. However, subsets of DCs also induce immune-tolerance, leading to tumor immune escape. In this regard, the TME plays a major role in adversely affecting DC function. Better understanding of DC impairment mechanisms in the TME will lead to more efficient DC-targeting immunotherapy. Here, we review the different subtypes and functions of DCs in the TME, including conventional DCs, plasmacytoid DC and the newly proposed subset, mregDC. We further focus on how cancer cells modulate DCs to escape from the host’s immune-surveillance. Immune checkpoint expression, small molecule mediators, metabolites, deprivation of pro-immunogenic and release of pro-tumorigenic cytokine secretion by tumors and tumor-attracted immuno-suppressive cells inhibit DC differentiation and function. Finally, we discuss the impact of established therapies on DCs, such as immune checkpoint blockade. Creative DC-targeted therapeutic strategies will be highlighted, including cancer vaccines and cell-based therapies.