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乳腺癌的免疫治疗。

Immunotherapy in Breast Cancer.

机构信息

National Center for Tumour Diseases and Department of Obstetrics and Gynaecology, University Hospital Heidelberg, Heidelberg, Germany.

出版信息

Oncol Res Treat. 2016;39(6):335-45. doi: 10.1159/000446340. Epub 2016 May 25.

Abstract

The importance of the tumor microenvironment including immune cell infiltrates in breast cancer has long been recognized. Tumor-infiltrating lymphocytes are prognostic and predictive; however, their prevalence as well as their prognostic and predictive power are subtype-dependent and appear most prominent in aggressive subtypes like triple-negative and HER2-positive disease. The immune responses observed in many cancers are attracted by tumor-associated antigens and, as suggested by recent research, by neoantigens - immunogenic antigens encoded for by non-synonymous mutations. The appealing promise of cancer vaccines has been pursued in breast cancer for over 2 decades; however, despite much effort having been put into vaccine trials, their clinical benefit, with the exception of some encouraging preliminary results, remains disappointing. The main hurdles compromising the efficacy of these vaccination strategies are the difficulties to generate broad and robust immune responses as well as to overcome immune escape mechanisms. The remarkable efficacy of immune checkpoint inhibitors in melanoma and lung cancer has set the ground for a race in the clinical development of numerous agents targeting these immune escape mechanisms in many tumor entities. Early clinical data in metastatic breast cancer suggests at least some clinical activity. This review discusses the current status and future perspectives of immunotherapy in breast cancer.

摘要

肿瘤微环境(包括免疫细胞浸润)在乳腺癌中的重要性早已被认识到。肿瘤浸润淋巴细胞具有预后和预测价值;然而,其普遍性以及其预后和预测能力取决于亚型,在三阴性和 HER2 阳性等侵袭性亚型中最为明显。许多癌症中观察到的免疫反应是由肿瘤相关抗原引起的,而且正如最近的研究表明的那样,是由新抗原引起的——由非同义突变编码的免疫原性抗原。癌症疫苗的诱人前景在乳腺癌中已经追求了 20 多年;然而,尽管在疫苗试验上投入了大量的努力,除了一些令人鼓舞的初步结果外,其临床获益仍然令人失望。这些疫苗接种策略的疗效主要受到以下两个方面的阻碍:难以产生广泛而强大的免疫反应,以及难以克服免疫逃逸机制。免疫检查点抑制剂在黑色素瘤和肺癌中的显著疗效为针对许多肿瘤实体中这些免疫逃逸机制的众多药物的临床开发奠定了基础。转移性乳腺癌的早期临床数据表明至少有一些临床活性。本文讨论了乳腺癌免疫治疗的现状和未来展望。

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