放疗和免疫疗法联合治疗非小细胞肺癌：挑战与更新,Cancer Communications

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放疗和免疫疗法联合治疗非小细胞肺癌：挑战与更新
Cancer Communications ( IF 20.1 ) Pub Date : 2021-10-17 , DOI: 10.1002/cac2.12226
Shijie Shang ₁ , Jie Liu ₂ , Vivek Verma ₃ , Meng Wu ₂ , James Welsh ₃ , Jinming Yu _{1,

2} , Dawei Chen _{1,

2}

Affiliation

免疫疗法对晚期非小细胞肺癌 (NSCLC) 的疗效仍然不令人满意，因为大多数患者要么没有出现客观反应，要么获得继发性耐药。因此，已经研究了几种增强免疫治疗全身疗效的方法，包括通过将免疫治疗与放射治疗 (RT) 相结合进行的大范围积极研究。鉴于将免疫疗法和放疗相结合以增加治疗效果的概念迅速兴起，我们回顾了迄今为止该领域的进展，并探索了进一步增强这种组合的途径。本综述首先讨论了仅有的两项现有随机试验（和一项汇总分析），这些试验表明在免疫疗法中加入放疗可提高远隔反应率、无进展生存期、和转移性非小细胞肺癌患者的总生存期。然后，我们讨论了可能与额外放疗成比例更大获益相关的因素和生物标志物，例如低程序性细胞死亡蛋白配体 1 (PD-L1) 状态、肿瘤突变负荷 (TMB) 和患者的免疫功能。接下来，讨论了实施 RT 以克服免疫疗法耐药性，包括机制讨论和可以利用这些机制的方法。最后，讨论了低剂量放疗的新兴作用，这可能有助于克服肿瘤基质中限制 T 细胞浸润的抑制信号。综上所述，鉴于这一快速扩张领域的现状，这些未来战略可能会被反映在进一步提高免疫疗法对更广泛患者群体的疗效上。

"点击查看英文标题和摘要"

Combined treatment of non-small cell lung cancer using radiotherapy and immunotherapy: challenges and updates

The efficacy of immunotherapy for advanced non-small cell lung cancer (NSCLC) remains unsatisfactory, as the majority of patients either do not experience an objective response or acquire secondary resistance. As a result, several methods to enhance the systemic efficacy of immunotherapy have been investigated, including a large area of active research by combining immunotherapy with radiation therapy (RT). Given the rapidly burgeoning concept of combining immunotherapy and RT for increasing therapeutic benefit, we review the progress in this field thus far and explore further avenues for enhancing this combination. This review commences with a discussion of the only two existing randomized trials (and a pooled analysis) showing that the addition of RT to immunotherapy improves the abscopal response rate, progression-free survival, and overall survival in metastatic NSCLC patients. We then discussed factors and biomarkers that may be associated with a proportionally greater benefit to additional RT, such as low programmed cell death protein ligand 1 (PD-L1) status, tumor mutational burden (TMB), and patient's immune function. Next, the implementation of RT to overcome immunotherapy resistance is discussed, including a mechanistic discussion and methods with which these mechanisms could be exploited. Lastly, the emerging role of low-dose RT is discussed, which may help to overcome inhibitory signals in the tumor stroma that limit T-cell infiltration. Taken together, given the current state of this rapidly expanding realm, these futuristic strategies may be reflected upon to further enhance the efficacy of immunotherapy for a wider group of patients.

更新日期：2021-11-27

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