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探索胰腺癌的新型系统疗法:新兴抗 PD-1/PD-L1 联合疗法综述。

Exploring novel systemic therapies for pancreatic cancer: a review of emerging anti-PD-1/PD-L1 combination therapy.

机构信息

Xinxiang Medical University, Henan, China.

Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Neoplasma. 2022 Sep;69(5):995-1007. doi: 10.4149/neo_2022_220306N246. Epub 2022 Jun 30.

Abstract

Despite attempts to apply single therapy such as surgical treatment, chemotherapy, or radiotherapy, pancreatic cancer (PC) is still one of the most lethal solid tumors. Moreover, immune checkpoint inhibitors against PD-1/PD-L1, which have shown good efficacies against many other solid tumors, have not shown encouraging results in PC treatment. Therefore, some studies are evaluating the efficacies of combination therapies based on anti-PD-1/PD-L1 for PC. In this review, we summarized the emerging anti-PD-1/PD-L1 combination therapies for PC in these years. We realized that anti-PD-1/PD-L1-based combination therapies have the potential to be efficacious in PC treatment, and further relevant studies are needed. Moreover, we elucidated the reasons for the ineffectiveness of anti-PD-1/PD-L1 alone in PC treatment. We concluded that this was mainly because PC has an immunosuppressive tumor microenvironment and develops drug resistance during treatment. Anti-PD-1/PD-L1-based combination therapeutic regimens that alter the immunosuppressive tumor microenvironment and reduce the development of drug resistance in PC are summarized in this review, and we expect that these regimens will achieve good clinical application prospects.

摘要

尽管尝试了单一疗法,如手术治疗、化疗或放疗,但胰腺癌(PC)仍然是最致命的实体肿瘤之一。此外,针对 PD-1/PD-L1 的免疫检查点抑制剂在许多其他实体肿瘤的治疗中显示出了良好的疗效,但在 PC 的治疗中并未显示出令人鼓舞的结果。因此,一些研究正在评估基于抗 PD-1/PD-L1 的联合疗法在 PC 中的疗效。在这篇综述中,我们总结了近年来针对 PC 的新兴抗 PD-1/PD-L1 联合疗法。我们意识到,基于抗 PD-1/PD-L1 的联合疗法有可能在 PC 治疗中有效,需要进一步开展相关研究。此外,我们还阐明了抗 PD-1/PD-L1 单独治疗在 PC 中无效的原因。我们得出的结论是,这主要是因为 PC 具有免疫抑制性肿瘤微环境,并在治疗过程中产生耐药性。本综述总结了改变 PC 中免疫抑制性肿瘤微环境和减少耐药性发展的基于抗 PD-1/PD-L1 的联合治疗方案,我们期望这些方案将获得良好的临床应用前景。

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