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化疗在乳腺癌中的免疫刺激作用:从免疫原性调节机制到临床实践。

Immunostimulatory Properties of Chemotherapy in Breast Cancer: From Immunogenic Modulation Mechanisms to Clinical Practice.

机构信息

Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, China.

出版信息

Front Immunol. 2022 Jan 5;12:819405. doi: 10.3389/fimmu.2021.819405. eCollection 2021.

Abstract

Breast cancer (BC) is the most common malignancy among females. Chemotherapy drugs remain the cornerstone of treatment of BC and undergo significant shifts over the past 100 years. The advent of immunotherapy presents promising opportunities and constitutes a significant complementary to existing therapeutic strategies for BC. Chemotherapy as a cytotoxic treatment that targets proliferation malignant cells has recently been shown as an effective immune-stimulus in multiple ways. Chemotherapeutic drugs can cause the release of damage-associated molecular patterns (DAMPs) from dying tumor cells, which result in long-lasting antitumor immunity by the key process of immunogenic cell death (ICD). Furthermore, Off-target effects of chemotherapy on immune cell subsets mainly involve activation of immune effector cells including natural killer (NK) cells, dendritic cells (DCs), and cytotoxic T cells, and depletion of immunosuppressive cells including Treg cells, M2 macrophages and myeloid-derived suppressor cells (MDSCs). Current mini-review summarized recent large clinical trials regarding the combination of chemotherapy and immunotherapy in BC and addressed the molecular mechanisms of immunostimulatory properties of chemotherapy in BC. The purpose of our work was to explore the immune-stimulating effects of chemotherapy at the molecular level based on the evidence from clinical trials, which might be a rationale for combinations of chemotherapy and immunotherapy in BC.

摘要

乳腺癌(BC)是女性中最常见的恶性肿瘤。化疗药物仍然是 BC 治疗的基石,在过去的 100 年中经历了重大转变。免疫疗法的出现带来了有希望的机会,并构成了 BC 现有治疗策略的重要补充。化疗作为一种针对增殖恶性细胞的细胞毒性治疗方法,最近已被证明在多种方式下是一种有效的免疫刺激物。化疗药物可以导致死亡的肿瘤细胞释放损伤相关分子模式(DAMPs),通过免疫原性细胞死亡(ICD)的关键过程导致持久的抗肿瘤免疫。此外,化疗对免疫细胞亚群的脱靶效应主要涉及免疫效应细胞的激活,包括自然杀伤(NK)细胞、树突状细胞(DC)和细胞毒性 T 细胞,以及免疫抑制细胞的耗竭,包括调节性 T 细胞(Treg)、M2 巨噬细胞和髓源性抑制细胞(MDSC)。目前的小型综述总结了最近关于 BC 中化疗和免疫疗法联合的大型临床试验,并讨论了化疗在 BC 中具有免疫刺激特性的分子机制。我们的工作目的是基于临床试验的证据,从分子水平探索化疗的免疫刺激作用,这可能是 BC 中化疗和免疫疗法联合的合理依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f19/8766762/df220204dbea/fimmu-12-819405-g001.jpg

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