Sanchez Katherine, Page David, McArthur Heather L
Providence Cancer Center / Earle A. Chiles Research Institute, Portland, OR.
Cedars-Sinai Medical Center, Los Angeles, CA.
Curr Probl Cancer. 2016 Mar-Aug;40(2-4):151-162. doi: 10.1016/j.currproblcancer.2016.09.009. Epub 2016 Sep 26.
Immune therapy has recently emerged as a standard-of-care strategy for the treatment of melanoma, lung cancer, bladder cancer, among other malignancies. However, the role of immune therapy in the treatment of breast cancer is still being determined. Two current strategies for harnessing the immune system to treat cancer include drugs that modulate key T cell inhibitory checkpoints and vaccines. Specifically, modern immune therapy strategies can facilitate T-cell mediated tumor regression by priming the immune system against specific tumor associated antigens, by modulating immunoregulatory signals, or both. In breast cancer, preliminary data from preclinical and early clinical studies are promising. In fact, clinical data with checkpoint blockade as monotherapy has been reported in multiple breast cancer subtypes to date, with durable responses observed in a significant proportion of women with chemotherapy resistant disease. However, because the number of genetic mutations and thus, the number of neoantigens available for immune response are modest in most breast cancers when compared with other cancers, most breast cancers may not be inherently sensitive to immune modulation and therefore may require strategies that enhance tumor associated antigen presentation if immune modulation strategies are to be effective. To that end, studies that combine checkpoint blockade with other strategies including established systemic therapies (including hormone therapy and chemotherapy), radiation therapy, and localized therapy including tumor freezing (cryoablation) are underway in breast cancer. Studies that combine checkpoint blockade with vaccines are also planned. Herein, we provide a brief summary of key components of the immune response against cancer, a rationale for the use of immune therapy in breast cancer, data from early clinical trials of checkpoint blockade and vaccine strategies in breast cancer, and future directions in the field.
免疫疗法最近已成为治疗黑色素瘤、肺癌、膀胱癌等多种恶性肿瘤的标准治疗策略。然而,免疫疗法在乳腺癌治疗中的作用仍在确定中。目前利用免疫系统治疗癌症的两种策略包括调节关键T细胞抑制性检查点的药物和疫苗。具体而言,现代免疫疗法策略可通过启动免疫系统针对特定肿瘤相关抗原、调节免疫调节信号或两者兼而有之,促进T细胞介导的肿瘤消退。在乳腺癌中,临床前和早期临床研究的初步数据很有前景。事实上,迄今为止,在多种乳腺癌亚型中都报道了以检查点阻断作为单一疗法的临床数据,在相当一部分化疗耐药的女性患者中观察到了持久反应。然而,与其他癌症相比,大多数乳腺癌的基因突变数量以及因此可用于免疫反应的新抗原数量较少,大多数乳腺癌可能对免疫调节并非固有敏感,因此如果免疫调节策略要有效,可能需要增强肿瘤相关抗原呈递的策略。为此,将检查点阻断与其他策略相结合的研究正在乳腺癌中开展,这些策略包括既定的全身疗法(包括激素疗法和化疗)、放射疗法以及包括肿瘤冷冻(冷冻消融)在内的局部疗法。将检查点阻断与疫苗相结合的研究也在计划之中。在此,我们简要总结了针对癌症的免疫反应的关键组成部分、在乳腺癌中使用免疫疗法的基本原理、乳腺癌中检查点阻断和疫苗策略的早期临床试验数据以及该领域的未来方向。
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