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突破障碍:三阴性乳腺癌中免疫检查点抑制剂的前景与挑战

Breaking Barriers: The Promise and Challenges of Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer.

作者信息

Said Sawsan Sudqi, Ibrahim Wisam Nabeel

机构信息

Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha P.O. Box 2713, Qatar.

出版信息

Biomedicines. 2024 Feb 5;12(2):369. doi: 10.3390/biomedicines12020369.

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with pronounced immunogenicity, exhibiting rapid proliferation and immune cell infiltration into the tumor microenvironment. TNBC's heterogeneity poses challenges to immunological treatments, inducing resistance mechanisms in the tumor microenvironment. Therapeutic modalities, including immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, and CTLA-4, are explored in preclinical and clinical trials. Promising results emerge from combining ICIs with anti-TGF-β and VISTA, hindering TNBC tumor growth. TNBC cells employ complex evasion strategies involving interactions with stromal and immune cells, suppressing immune recognition through various cytokines, chemokines, and metabolites. The recent focus on unraveling humoral and cellular components aims to disrupt cancer crosstalk within the tumor microenvironment. This review identifies TNBC's latest resistance mechanisms, exploring potential targets for clinical trials to overcome immune checkpoint resistance and enhance patient survival rates.

摘要

三阴性乳腺癌(TNBC)是一种具有高度侵袭性的恶性肿瘤,具有显著的免疫原性,表现出快速增殖以及免疫细胞浸润至肿瘤微环境中。TNBC的异质性给免疫治疗带来了挑战,在肿瘤微环境中诱导出耐药机制。包括靶向PD-1、PD-L1和CTLA-4的免疫检查点抑制剂(ICI)在内的治疗方式正在临床前和临床试验中进行探索。将ICI与抗TGF-β和VISTA联合使用产生了有前景的结果,可阻碍TNBC肿瘤生长。TNBC细胞采用复杂的逃避策略,涉及与基质细胞和免疫细胞的相互作用,通过各种细胞因子、趋化因子和代谢产物抑制免疫识别。最近对揭示体液和细胞成分的关注旨在破坏肿瘤微环境内的癌症串扰。本综述确定了TNBC的最新耐药机制,探索临床试验的潜在靶点,以克服免疫检查点耐药并提高患者生存率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0f8/10886684/533a8ca311ff/biomedicines-12-00369-g001.jpg

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