Targeting immune cells in tumor microenvironment in triple negative breast cancer therapy: future perspective to overcome doxorubicin resistance and toxicity

Triple negative breast cancer (TNBC) has high recurrence and low survival rates among breast cancer types. So far, TNBC treatment has been limited to chemotherapy, which leads to high recurrence and drug resistance. The immune cells in the tumor microenvironment (TME) play an important role in tumor development and cancer progression. This study aimed to explore how immune cells in TME have been used to treat TNBC cases in combination with Doxorubicin (DOX). Searching was conducted for scientific publications on several databases in the past 10 years (2013-2023). Of the 7622 articles, 14 articles met the inclusion criteria and underwent the extraction process. All articles extracted in this review were preclinical studies on experimental animals. The results indicate the combination of DOX with cyclophosphamide and aminoglutethimide, increasing CD8 + infiltration resulting in tumor growth inhibition. The combination of DOX with vorinostat and molecular PepO also induces anti-tumor activity in the TME via increased infiltration of B cells and T cells and induced transition from M2 into M1. Other results, which lead to better prognosis have been obtained from the combination of DOX with losartan and anti-PD1 that leads to overhauling the immunosuppressive microenvironment. Targeting immune cells in TME such as dendritic cells, tumor-associated macrophages, CD8 + and CD4 + T cells are potentially used as therapeutic targets for TNBC treatment to optimize anti-tumor activity using combinations of DOX and certain drugs. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.