Immune evasion and resistance in breast cancer.

Abstract

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.