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抗原加工与呈递在癌症中的作用及免疫检查点抑制剂免疫疗法的疗效

The Role of Antigen Processing and Presentation in Cancer and the Efficacy of Immune Checkpoint Inhibitor Immunotherapy.

作者信息

Mpakali Anastasia, Stratikos Efstratios

机构信息

National Centre for Scientific Research Demokritos, Agia Paraskevi, 15341 Athens, Greece.

Laboratory of Biochemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zographou, 15784 Athens, Greece.

出版信息

Cancers (Basel). 2021 Jan 4;13(1):134. doi: 10.3390/cancers13010134.

Abstract

Recent clinical successes of cancer immunotherapy using immune checkpoint inhibitors (ICIs) are rapidly changing the landscape of cancer treatment. Regardless of initial impressive clinical results though, the therapeutic benefit of ICIs appears to be limited to a subset of patients and tumor types. Recent analyses have revealed that the potency of ICI therapies depends on the efficient presentation of tumor-specific antigens by cancer cells and professional antigen presenting cells. Here, we review current knowledge on the role of antigen presentation in cancer. We focus on intracellular antigen processing and presentation by Major Histocompatibility class I (MHCI) molecules and how it can affect cancer immune evasion. Finally, we discuss the pharmacological tractability of manipulating intracellular antigen processing as a complementary approach to enhance tumor immunogenicity and the effectiveness of ICI immunotherapy.

摘要

近期使用免疫检查点抑制剂(ICI)进行癌症免疫治疗所取得的临床成功正在迅速改变癌症治疗的格局。尽管最初的临床结果令人印象深刻,但ICI的治疗益处似乎仅限于一部分患者和肿瘤类型。最近的分析表明,ICI疗法的效力取决于癌细胞和专职抗原呈递细胞对肿瘤特异性抗原的有效呈递。在此,我们综述了目前关于抗原呈递在癌症中作用的知识。我们重点关注主要组织相容性复合体I类(MHCI)分子介导的细胞内抗原加工和呈递,以及它如何影响癌症免疫逃逸。最后,我们讨论了将操纵细胞内抗原加工作为一种补充方法来增强肿瘤免疫原性和ICI免疫治疗效果的药理学可操作性。

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