Aptamer-Based Strategies to Boost Immunotherapy in TNBC

Simple Summary Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor outcomes and limited therapeutic options. It is characterized by a more pronounced immunogenicity compared with other breast cancer subtypes, suggesting immunotherapy is a viable strategy. Aptamers are short oligonucleotides that, similar to antibodies, recognize their protein target with high specificity and affinity. However, compared with antibodies, they present several advantages in terms of size, production, modification, and stability, which make them excellent candidates for the development of novel targeted anticancer therapies. Recently, in order to restore an immunoreactive and anticancer tumor microenvironment, effective aptamer-based strategies have been developed. Here, we discuss the most recent approaches aimed at using aptamers to enhance or restore the anticancer immune response in TNBC.The immune system (IS) may play a crucial role in preventing tumor development and progression, leading, over the last years, to the development of effective cancer immunotherapies. Nevertheless, immune evasion, the capability of tumors to circumvent destructive host immunity, remains one of the main obstacles to overcome for maximizing treatment success. In this context, promising strategies aimed at reshaping the tumor immune microenvironment and promoting antitumor immunity are rapidly emerging. Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype with poor outcomes, is highly immunogenic, suggesting immunotherapy is a viable strategy. As evidence of this, already, two immunotherapies have recently become the standard of care for patients with PD-L1 expressing tumors, which, however, represent a low percentage of patients, making more active immunotherapeutic approaches necessary. Aptamers are short, highly structured, single-stranded oligonucleotides that bind to their protein targets at high affinity and specificity. They are used for therapeutic purposes in the same way as monoclonal antibodies; thus, various aptamer-based strategies are being actively explored to stimulate the IS's response against cancer cells. The aim of this review is to discuss the potential of the recently reported aptamer-based approaches to boost the IS to fight TNBC.