Immunotherapy in breast cancer.
Immunotherapy in breast cancer.
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DOI：
10.4103/jcar.jcar_2_19
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发表时间：
2019-01-01
影响因子：
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通讯作者：
Gluck, Stefan
中科院分区：
文献类型：
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作者：
Bayraktar, Soley;Batoo, Sameer;Gluck, Stefan
利用免疫系统对抗癌症的想法已有100多年的历史。一种新的分子方法导致了对免疫系统的更好理解。检查点调节，理解Tcl 4，Th 1和Th 2的作用，嵌合抗原受体（CAR）-T细胞的发展，以及树突状细胞和巨噬细胞的调节，只是我们理解的几个例子，也导致了免疫检查点抑制剂（ICI）和调节剂的发现。这导致诺贝尔奖委员会在2018年授予James P. Allison博士细胞毒性T淋巴细胞相关抗原-4的发现诺贝尔医学奖，以及Tasuku Honjo博士发现程序性细胞死亡-1（PD-1）/PD-1-配体（PDL-1）。几种ICI已经获得监管机构的批准，目前有更多的ICI用于几种实体瘤和血液恶性肿瘤的研究。积极的研究已经导致美国食品和药物管理局（FDA）和欧洲药品管理局批准了许多这些化合物，但迄今为止还没有批准用于乳腺癌（BC）。此外，PD-1/PDL-1、MSI高（和dMMR）和肿瘤突变负荷是目前从免疫治疗中获益的“最佳”预测标志物。BC仅在子集中具有这些标志物中的一些阳性，但表达频率低于大多数其他实体瘤，例如恶性黑色素瘤或非小细胞肺癌。为了提高ICI治疗BC的潜在疗效，加用化疗是策略之一。许多早期和大型临床试验的所有阶段正在不列颠哥伦比亚省进行。我们将讨论免疫系统在BC编辑中的作用，以及免疫疗法对BC结果的潜在影响。
The idea of using the immune system to fight cancer is over 100 years old. A new molecular approach led to a better understanding of the immune system. Checkpoint regulation, understanding the roles of Tregs, Th1, and Th2, development of Chimeric antigen receptor (CAR)-T cells, as well as regulation of dendritic cells and macrophages, are just a few examples of our understating that has also led to the discovery of immune checkpoint inhibitors (ICIs) and modulators. This led the Nobel Prize committee in 2018, to award Dr. James P. Allison the Nobel Prize in medicine for the discovery of Cytotoxic T-lymphocyte-associated antigen-4, and Dr. Tasuku Honjo for the discovery of programmed cell death-1 (PD-1)/PD-1-ligand (PDL-1). Several ICIs are already approved by the regulatory authorities, and many more are currently used in studies of several solid tumors and hematologic malignancies. Positive studies have led to the US Food and Drug Administration (FDA) and European Medicines Agency approval of a number of these compounds, but none to date are approved in breast cancer (BC). Moreover, PD-1/PDL-1, MSI high (and dMMR), and tumor mutational burden are the currently "best" predictive markers for benefit from immunotherapy. BCs have some of these markers positive only in subsets but less frequently expressed than most other solid tumors, for example, malignant melanoma or non-small cell lung cancer. To improve the potential efficacy of ICI in BC, the addition of chemotherapy was one of the strategies. Many early and large clinical trials in all phases are underway in BC. We will discuss the role of immune system in BC editing, and the potential impact of immunotherapy in BC outcomes.