Down-regulation of immune checkpoints by doxorubicin and carboplatin-containing neoadjuvant regimens in a murine breast cancer model

Autor: Sanambar Sadighi, Ramezanali Sharifian, Monireh Kazemimanesh, Ahad Muhammadnejad, Zahra Shohosseini, Saeid Amanpour, Samad Muhammadnejad
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Iranian Journal of Basic Medical Sciences, Vol 24, Iss 4, Pp 537-544 (2021)
Druh dokumentu: article
ISSN: 2008-3866
2008-3874
DOI: 10.22038/ijbms.2021.54383.12221
Popis: Objective(s): Immune checkpoint expression on tumor-infiltrating lymphocytes (TILs) has a correlation with the outcome of neoadjuvant chemotherapy (NAC) in breast cancer. However, the reciprocal effect of these regimens on the quality and quantity of immune checkpoints has hitherto not been addressed. We aimed to evaluate the impact of three NAC regimens on TILs and immune checkpoints in a murine triple-negative breast cancer model.Materials and Methods: Syngeneic model of locally-advanced breast cancer was established in immunocompetent mice using a 4T1 cell line. Tumor-bearing animals were treated with human-equivalent dosages of doxorubicin, paclitaxel, paclitaxel and carboplatin combination, and placebo. Infiltration of CD3+, CD8+, and FoxP3+ cells into the tumor was assessed by immunohistochemistry. Expression of immune checkpoints, including PD-1, CTLA-4, and TIM-3, was evaluated by real-time PCR.Results: Doxorubicin led to a significant (p
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