Ababneh Ebaa, Velez Sarah, Zhao Jihe
Burnett School of Biomedical Science, Medical College, University of Central Florida Orlando, FL, USA.
Am J Cancer Res. 2025 Apr 15;15(4):1517-1539. doi: 10.62347/PNGT6996. eCollection 2025.
Breast cancer (BC) is the most common malignancy in females with an increasing incidence in the last decade. The previously observed decline in BC mortality rates has also slowed down recently with an increase in the incidence of invasive BC. BC has various molecular subtypes. Among these subtypes, triple-negative breast cancer (TNBC) represents the most aggressive BC, with a poor prognosis. Because lack of the hormonal or human epidermal growth factor receptor 2 (HER2) receptors, TNBC is resistant to hormonal and HER2 targeted therapy effective for other BC subtypes. The good news is that TNBC has recently been considered an immunologically 'hot' tumor. Therefore, immunotherapy, particularly immune checkpoint inhibitor therapy, represents a promising therapeutic approach TNBC. However, a considerable percentage of patients with TNBC do not respond well to immunotherapy, indicating that TNBC seems to adopt several mechanisms to evade immune surveillance. Thus, it is crucial to investigate the mechanisms underlying TNBC immune evasion and resistance to immunotherapy. In this review, we examine and discuss the most recently discovered mechanisms for BC, with a particular focus on TNBC, to evade the immune surveillance via kidnapping the immune checkpoints, suppressing the immune responses in tumor microenvironment and inhibiting the tumor antigen presentation. Evaluation of these mechanisms in BC will hopefully guide future immunotherapeutic research and clinical trials.
乳腺癌(BC)是女性中最常见的恶性肿瘤,在过去十年中发病率不断上升。之前观察到的乳腺癌死亡率下降趋势最近也有所放缓,同时浸润性乳腺癌的发病率有所增加。乳腺癌有多种分子亚型。在这些亚型中,三阴性乳腺癌(TNBC)是最具侵袭性的乳腺癌,预后较差。由于缺乏激素或人表皮生长因子受体2(HER2)受体,TNBC对其他乳腺癌亚型有效的激素和HER2靶向治疗具有抗性。好消息是,TNBC最近被认为是一种免疫“热”肿瘤。因此,免疫疗法,特别是免疫检查点抑制剂疗法,是TNBC一种有前景的治疗方法。然而,相当比例的TNBC患者对免疫疗法反应不佳,这表明TNBC似乎采用了多种机制来逃避免疫监视。因此,研究TNBC免疫逃逸和对免疫疗法耐药的潜在机制至关重要。在这篇综述中,我们研究并讨论了乳腺癌,特别是TNBC,通过劫持免疫检查点、抑制肿瘤微环境中的免疫反应以及抑制肿瘤抗原呈递来逃避免疫监视的最新发现机制。对乳腺癌中这些机制的评估有望指导未来的免疫治疗研究和临床试验。