Schmidt Marcus, Heimes Anne-Sophie
Department of Obstetrics and Gynecology, University Medical Center Mainz, 55131 Mainz, Germany.
Cancers (Basel). 2021 Sep 29;13(19):4883. doi: 10.3390/cancers13194883.
The role of the immune system in breast cancer has been debated for decades. The advent of technologies such as next generation sequencing (NGS) has elucidated the crucial interplay between somatic mutations in tumors leading to neoantigens and immune responses with increased tumor-infiltrating lymphocytes and improved prognosis of breast cancer patients. In particular, triple-negative breast cancer (TNBC) has a higher mutational burden compared to other breast cancer subtypes. In addition, higher levels of tumor-associated antigens suggest that immunotherapies are a promising treatment option, specifically for TNBC. Indeed, higher concentrations of tumor-infiltrating lymphocytes are associated with better prognosis and response to chemotherapy in TNBC. An important target within the cancer immune cell cycle is the "immune checkpoint". Immune checkpoint inhibitors (ICPis) block the interaction of certain cell surface proteins that act as "brakes" on immune responses. Recent studies have shown that ICPis improve survival in both early and advanced TNBC. However, this comes at the price of increased toxicity, particularly immune-mediated toxicity. As an alternative approach, individualized mRNA vaccination strategies against tumor-associated neoantigens represent another promising approach leading to neoantigen-specific immune responses. These novel strategies should help to improve treatment outcomes, especially for patients with triple negative breast cancer.
免疫系统在乳腺癌中的作用已经争论了数十年。下一代测序（NGS）等技术的出现阐明了肿瘤体细胞突变导致新抗原与免疫反应之间的关键相互作用，这种相互作用表现为肿瘤浸润淋巴细胞增加以及乳腺癌患者预后改善。特别是，三阴性乳腺癌（TNBC）与其他乳腺癌亚型相比具有更高的突变负荷。此外，更高水平的肿瘤相关抗原表明免疫疗法是一种有前景的治疗选择，尤其是对TNBC。确实，更高浓度的肿瘤浸润淋巴细胞与TNBC更好的预后及对化疗的反应相关。癌症免疫细胞周期中的一个重要靶点是“免疫检查点”。免疫检查点抑制剂（ICPis）阻断某些作为免疫反应“刹车”的细胞表面蛋白之间的相互作用。最近的研究表明，ICPis可提高早期和晚期TNBC患者的生存率。然而，这是以毒性增加为代价的，尤其是免疫介导的毒性。作为一种替代方法，针对肿瘤相关新抗原的个性化mRNA疫苗接种策略代表了另一种有前景的方法，可引发新抗原特异性免疫反应。这些新策略应有助于改善治疗效果，特别是对于三阴性乳腺癌患者。
