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新辅助免疫检查点阻断:推进癌症免疫治疗的机会之窗。

Neoadjuvant immune checkpoint blockade: A window of opportunity to advance cancer immunotherapy.

机构信息

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

出版信息

Cancer Cell. 2023 Sep 11;41(9):1551-1566. doi: 10.1016/j.ccell.2023.07.011. Epub 2023 Aug 17.

Abstract

Among new treatment approaches for patients with cancer, few have accelerated as quickly as neoadjuvant immune checkpoint blockade (ICB). Neoadjuvant cancer therapy is administered before curative-intent surgery in treatment-naïve patients. Conventional neoadjuvant chemotherapy and radiotherapy are primarily intended to reduce tumor size, improving surgical resectability. However, recent scientific evidence outlined here suggests that neoadjuvant immunotherapy can expand and transcriptionally modify tumor-specific T cell clones to enhance both intratumoral and systemic anti-tumor immunity. It further offers a unique "window of opportunity" to explore mechanisms and identify novel biomarkers of ICB response and resistance, opening possibilities for refining long-term clinical outcome predictions and developing new, more highly effective ICB combination therapies. Here, we examine advances in clinical and scientific knowledge gleaned from studies in select cancers and describe emerging key principles relevant to neoadjuvant ICB across many cancer types.

摘要

在癌症患者的新治疗方法中,很少有像新辅助免疫检查点阻断(ICB)那样快速发展的。新辅助癌症治疗是在未经治疗的患者接受根治性手术前进行的。传统的新辅助化疗和放疗主要旨在缩小肿瘤大小,提高手术可切除性。然而,这里概述的最新科学证据表明,新辅助免疫疗法可以扩增和转录修饰肿瘤特异性 T 细胞克隆,以增强肿瘤内和全身抗肿瘤免疫。它进一步提供了一个独特的“机会之窗”,可以探索机制,并确定新的免疫检查点抑制剂反应和耐药性的生物标志物,为改进长期临床结果预测和开发新的、更有效的免疫检查点抑制剂联合治疗提供了可能性。在这里,我们研究了从特定癌症研究中获得的临床和科学知识的进展,并描述了与许多癌症类型的新辅助免疫检查点相关的新兴关键原则。

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