新辅助免疫检查点阻断剂：推进癌症免疫治疗的机会之窗

SCI

9 September 2023

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

(Cancer Cell, IF: 50.3)

Suzanne L. Topalian, Patrick M. Forde, Leisha A. Emens, Mark Yarchoan, Kellie N. Smith, and Drew M. Pardoll

Correspondence To: stopali1@jhmi.edu (S.L.T.), dpardol1@jhmi.edu (D.M.P.)

SUMMARY 摘要

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-naive 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.

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剂（ICB）那样快速发展的治疗方法。癌症新辅助治疗是在初治患者的治疗性手术前进行的。传统的新辅助化疗和放疗主要是为了缩小肿瘤大小，提高手术可切除性。然而，最近的科学证据表明，新辅助免疫疗法可以扩展和转录修饰肿瘤特异性T细胞克隆，以增强肿瘤内和系统抗肿瘤免疫。它为进一步探索ICB反应和耐药性的机制和识别新的生物标志物提供了一个独特的“机会之窗”，为完善长期临床结果预测和开发新的更高效的ICB联合疗法开辟了可能性。在这里，我们研究了从选定癌症的研究中收集的临床和科学研究的进展，并描述了与许多癌症类型的新辅助ICB相关的新兴关键原则。

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