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作为靶向癌症治疗的免疫抑制信号通路

Immunosuppressive Signaling Pathways as Targeted Cancer Therapies.

作者信息

Setlai Botle Precious, Hull Rodney, Bida Meshack, Durandt Chrisna, Mulaudzi Thanyani Victor, Chatziioannou Aristotelis, Dlamini Zodwa

机构信息

Department of Surgery, Faculty of Health Sciences, University of Pretoria, Private Bag X323, Arcadia 0007, South Africa.

SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Hatfield 0028, South Africa.

出版信息

Biomedicines. 2022 Mar 16;10(3):682. doi: 10.3390/biomedicines10030682.

Abstract

Immune response has been shown to play an important role in defining patient prognosis and response to cancer treatment. Tumor-induced immunosuppression encouraged the recent development of new chemotherapeutic agents that assists in the augmentation of immune responses. Molecular mechanisms that tumors use to evade immunosurveillance are attributed to their ability to alter antigen processing/presentation pathways and the tumor microenvironment. Cancer cells take advantage of normal molecular and immunoregulatory machinery to survive and thrive. Cancer cells constantly adjust their genetic makeup using several mechanisms such as nucleotide excision repair as well as microsatellite and chromosomal instability, thus giving rise to new variants with reduced immunogenicity and the ability to continue to grow without restrictions. This review will focus on the central molecular signaling pathways involved in immunosuppressive cells and briefly discuss how cancer cells evade immunosurveillance by manipulating antigen processing cells and related proteins. Secondly, the review will discuss how these pathways can be utilized for the implementation of precision medicine and deciphering drug resistance.

摘要

免疫反应在确定患者预后和对癌症治疗的反应中发挥着重要作用。肿瘤诱导的免疫抑制推动了有助于增强免疫反应的新型化疗药物的近期发展。肿瘤用于逃避免疫监视的分子机制归因于它们改变抗原加工/呈递途径和肿瘤微环境的能力。癌细胞利用正常的分子和免疫调节机制来生存和发展。癌细胞通过多种机制不断调整其基因组成,如核苷酸切除修复以及微卫星和染色体不稳定性,从而产生免疫原性降低且能够不受限制地继续生长的新变体。本综述将聚焦于免疫抑制细胞中涉及的核心分子信号通路,并简要讨论癌细胞如何通过操纵抗原加工细胞和相关蛋白来逃避免疫监视。其次,本综述将讨论如何利用这些途径来实施精准医学和解读耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9300/8945019/4b1fa4dd18b2/biomedicines-10-00682-g001.jpg

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