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TIGIT 和 PD-1/PD-L1 通路的双重阻断为卵巢癌患者带来新希望

英文原题:The Dual Blockade of the TIGIT and PD-1/PD-L1 Pathway as a New Hope for Ovarian Cancer Patients.

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The Dual Blockade of the TIGIT and PD-1/PD-L1 Pathway as a New Hope for Ovarian Cancer Patients.

PubMed 2022/11/23(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

卵巢癌(OC)患者的预后较差,五年生存率仅为47%。免疫检查点(ICP)似乎是新兴OC治疗中的潜在靶点。然而,OC患者对基于程序性细胞死亡通路(PD-1/PD-L1)抑制剂的免疫治疗缓解率总计仅为6-15%。有前景的方法是联合治疗,包括其他ICP,如T细胞免疫球蛋白和ITIM结构域/ CD155/ DNAX辅助分子-1(TIGIT/CD155/DNAM-1)轴。在结直肠癌小鼠模型中的临床前研究显示,PD-1/PD-L1和TIGIT的双重阻断使整个研究组获得缓解,而单一通路阻断仅使肿瘤消退。该方法可刺激T细胞和NK细胞的效应活性,并重新定向免疫系统对肿瘤的活性。

然而,对TIGIT和PD-1/PD-L1阻断协同作用的认识尚不充分。因此,本综述旨在总结目前关于TIGIT和PD-1/PD-L1双重阻断的作用方式及其对OC患者潜在益处的认识。考虑到这种联合治疗在恶性肿瘤(包括肺癌和结直肠癌)中的积极影响,它似乎是OC治疗中一种有前景的方法。

展开英文摘要原文

The prognosis for ovarian cancer (OC) patients is poor and the five-year survival rate is only 47%. Immune checkpoints (ICPs) appear to be the potential targets in up-and-coming OC treatment.

However, the response of OC patients to immunotherapy based on programmed cell death pathway (PD-1/PD-L1) inhibitors totals only 6-15%. The promising approach is a combined therapy, including other ICPs such as the T-cell immunoglobulin and ITIM domain/CD155/DNAX accessory molecule-1 (TIGIT/CD155/DNAM-1) axis.

Preclinical studies in a murine model of colorectal cancer showed that the dual blockade of PD-1/PD-L1 and TIGIT led to remission in the whole studied group vs. the regression of the tumors with the blockade of a single pathway. The approach stimulates the effector activity of T cells and NK cells, and redirects the immune system activity against the tumor. The understanding of the synergistic action of the TIGIT and PD-1/PD-L1 blockade is, however, poor.

Thus, the aim of this review is to summarize the current knowledge about the mode of action of the dual TIGIT and PD-1/PD-L1 blockade and its potential benefits for OC patients. Considering the positive impact of this combined therapy in malignancies, including lung and colorectal cancer, it appears to be a promising approach in OC treatment.

论文信息

作者
Pawłowska A、Skiba W、Suszczyk D、Kuryło W、Jakubowicz-Gil J、Paduch R、Wertel I
单位
Independent Laboratory of Cancer Diagnostics and Immunology, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland.Poland
文献类型
综述
期刊
Cancers2022 Nov 23
原文标识
PubMed 36497240 · DOI 10.3390/cancers14235757