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炎性小体与 PD-1/PD-L1 的相互作用及其在癌症免疫治疗中的意义。

Interplay between inflammasomes and PD-1/PD-L1 and their implications in cancer immunotherapy.

机构信息

Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology (Peking University), Peking University Health Science Center, Beijing 100191, P.R. China.

出版信息

Carcinogenesis. 2023 Dec 30;44(12):795-808. doi: 10.1093/carcin/bgad072.

Abstract

The inflammasomes play crucial roles in inflammation and cancer development, while the PD-1/PD-L1 pathway is critical for immune suppression in the tumor microenvironment (TME). Recent research indicates a reciprocal regulatory relationship between inflammasomes and PD-1/PD-L1 signaling in cancer development and PD-1 blockade treatment. By activating in diverse cells in tumor tissues, inflammasome upregulates PD-L1 level in the TME. Moreover, the regulation of PD-1/PD-L1 activity by inflammasome activation involves natural killer cells, tumor-associated macrophages and myeloid-derived suppressor cells. Conversely, PD-1 blockade can activate the inflammasome, potentially influencing treatment outcomes. The interplay between inflammasomes and PD-1/PD-L1 has profound and intricate effects on cancer development and treatment. In this review, we discuss the crosstalk between inflammasomes and PD-1/PD-L1 in cancers, exploring their implications for tumorigenesis, metastasis and immune checkpoint inhibitor (ICI) resistance. The combined therapeutic strategies targeting both inflammasomes and checkpoint molecules hold promising potential as treatments for cancer.

摘要

炎性小体在炎症和癌症发展中发挥着关键作用,而 PD-1/PD-L1 通路在肿瘤微环境 (TME) 中对免疫抑制至关重要。最近的研究表明,在癌症发展和 PD-1 阻断治疗中,炎性小体和 PD-1/PD-L1 信号之间存在着相互调节的关系。通过在肿瘤组织中的多种细胞中激活,炎性小体上调了 TME 中的 PD-L1 水平。此外,炎性小体激活对 PD-1/PD-L1 活性的调节涉及自然杀伤细胞、肿瘤相关巨噬细胞和髓系来源的抑制细胞。相反,PD-1 阻断可以激活炎性小体,这可能会影响治疗效果。炎性小体与 PD-1/PD-L1 之间的相互作用对癌症的发展和治疗有着深远而复杂的影响。在这篇综述中,我们讨论了炎性小体与 PD-1/PD-L1 在癌症中的相互作用,探讨了它们对肿瘤发生、转移和免疫检查点抑制剂 (ICI) 耐药性的影响。针对炎性小体和检查点分子的联合治疗策略作为癌症治疗具有很大的潜力。

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