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克服食管癌对PD-1/PD-L1抑制剂的耐药性。

Overcoming resistance to PD-1/PD-L1 inhibitors in esophageal cancer.

作者信息

Cheng Chao, Zhuge Lingdun, Xiao Xin, Luan Siyuan, Yuan Yong

机构信息

Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, China.

Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Front Oncol. 2022 Sep 5;12:955163. doi: 10.3389/fonc.2022.955163. eCollection 2022.

Abstract

As the predominant treatment option of the immunotherapy for advanced esophageal cancer (EC), the application of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors brings new hope to clinical practice. However, a considerable portion of patients do not response to this therapy, meanwhile most patients sensitive to PD-1 or PD-L1 antibody initially will develop resistance to the treatment eventually. To break through the limits of clinical effect, it is of critical importance to make a profound understanding of the mechanisms of so called primary resistance and acquired resistance. Subsequently, exploring potent predictors to identify suitable patients for anti-PD-1/PD-L1 treatment and investigating efficient strategies to overcome drug resistance will be helpful to expend the benefit of immunotherapy. In the present view, we summarized the potential predictive factors for anti-PD-1/PD-L1 immunotherapy in EC, and demonstrated the plausible mechanisms of resistance to PD-1/PD-L1 blockade as well as its feasible solutions.

摘要

作为晚期食管癌(EC)免疫治疗的主要选择,程序性死亡1(PD-1)和程序性死亡配体1(PD-L1)抑制剂的应用给临床实践带来了新希望。然而,相当一部分患者对这种治疗无反应,同时,大多数最初对PD-1或PD-L1抗体敏感的患者最终会对治疗产生耐药性。为突破临床疗效的限制,深入了解所谓原发性耐药和获得性耐药的机制至关重要。随后,探索有效的预测指标以识别适合抗PD-1/PD-L1治疗的患者,并研究克服耐药性的有效策略,将有助于扩大免疫治疗的获益。在当前观点中,我们总结了EC中抗PD-1/PD-L1免疫治疗的潜在预测因素,并阐述了对PD-1/PD-L1阻断耐药的合理机制及其可行的解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61c3/9483164/11ba73efe122/fonc-12-955163-g001.jpg

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