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靶向 PD-1/PD-L1 在癌症免疫治疗中的应用:治疗三阴性乳腺癌(TNBC)患者的有效策略

英文原题:Targeting PD-1/PD-L1 in cancer immunotherapy: An effective strategy for treatment of triple-negative breast cancer (TNBC) patients.

查看英文原题

Targeting PD-1/PD-L1 in cancer immunotherapy: An effective strategy for treatment of triple-negative breast cancer (TNBC) patients.

PubMed 2022/08/24(内容时间) Genes Dis Q1 · IF 14.6(JCR 2025)

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中文摘要

维持对外来蛋白产生免疫应答与耐受自身蛋白之间的平衡对于维持稳态至关重要。程序性死亡蛋白1(PD-1)及其配体程序性死亡配体1(PD-L1)的功能是抑制免疫应答,从而使过度反应的免疫细胞不会对自身细胞造成损伤。

然而,癌细胞劫持这一机制来削弱免疫细胞功能,并营造免疫抑制环境,从而助长其持续生长和增殖。过去几年中,癌症免疫治疗的快速发展为癌症治疗开辟了新途径。阻断PD-1和PD-L1已成为一种潜在策略,可恢复免疫细胞功能以高效对抗癌症。最初,免疫检查点单药治疗并不十分成功,使乳腺癌被认为免疫原性较低。尽管如此,近期报道支持乳腺癌中存在TIL(肿瘤浸润淋巴细胞)(TILs),这使其更适合PD-1/PD-L1介导的免疫治疗,而该治疗在PD-L1阳性患者中有效。最近,抗PD-1(pembrolizumab)和抗PD-L1(atezolizumab)获得FDA批准用于乳腺癌治疗,使PD-1/PD-L1免疫治疗对进一步研究具有重要意义。同样,本文汇集了近年来对PD-1和PD-L1的认识,它们的信号网络、与其他分子的相互作用、其在正常组织和肿瘤组织微环境中的表达与功能调控,对于发现和设计阻断该通路的治疗药物并提高治疗疗效至关重要。

此外,作者收集并强调了关于单药治疗和联合治疗的大多数重要临床试验报告。

展开英文摘要原文

Maintaining the balance between eliciting immune responses against foreign proteins and tolerating self-proteins is crucial for maintenance of homeostasis. The functions of programmed death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) are to inhibit immune responses so that over-reacting immune cells does not cause any damage to its own body cells.

However, cancer cells hijack this mechanism to attenuate immune cells functions and create an immunosuppressive environment that fuel their continuous growth and proliferation. Over the past few years' rapid development in cancer immunotherapy has opened a new avenue in cancer treatment. Blockade of PD-1 and PD-L1 has become a potential strategy that rescue the functions of immune cells to fight against cancer with high efficacy. Initially, immune checkpoint monotherapies were not very successful, making breast cancer less immunogenic.

Although, recent reports support the presence of tumor infiltrating lymphocytes (TILs) in breast cancer that make it favorable for PD-1/PD-L1 mediated immunotherapy, which is effective in PD-L1 positive patients. Recently, anti-PD-1 (pembrolizumab) and anti-PD-L1 (atezolizumab) gets FDA approval for breast cancer treatment and make PD-1/PD-L1 immunotherapy is meaningful for further research.

Likewise, this article gathered understanding of PD-1 and PD-L1 in recent years, their signaling networks, interaction with other molecules, regulations of their expressions and functions in both normal and tumor tissue microenvironments are crucial to find and design therapeutic agents that block this pathway and improve the treatment efficacy.

Additionally, authors collected and highlighted most of the important clinical trial reports on monotherapy and combination therapy.

论文信息

作者
Kumar S、Chatterjee M、Ghosh P、Ganguly KK、Basu M、Ghosh MK
单位
Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector-V, Salt Lake, Kolkata 700091, Jadavpur, Kolkata, PIN 700032, India.India
文献类型
综述
期刊
Genes & diseases2023 Jul
原文标识
PubMed 37397537 · DOI 10.1016/j.gendis.2022.07.024