Programmed Death Ligand 1 Modulation by Bacillus Calmette-Guérin and Toll-Like Receptor Agonists in Distinct Breast Cancer Cell Subtypes
Gabriela Barbosa,1,2 Maria Carolina Ximenes De Godoy,1 Caroline Cavalli Bighetto,1 Emily Macedo Skakum,1 Lívia Bitencourt Pascoal,1,2 Alessandra Gambero,1,2 Leonardo O Reis1– 3 1ImmunOOncology, Pontifical Catholic University of Campinas, Campinas, São Paul...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2025-06-01
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| Series: | International Journal of General Medicine |
| Subjects: | |
| Online Access: | https://www.dovepress.com/programmed-death-ligand-1-modulation-by-bacillus-calmette-gurin-and-to-peer-reviewed-fulltext-article-IJGM |
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| Summary: | Gabriela Barbosa,1,2 Maria Carolina Ximenes De Godoy,1 Caroline Cavalli Bighetto,1 Emily Macedo Skakum,1 Lívia Bitencourt Pascoal,1,2 Alessandra Gambero,1,2 Leonardo O Reis1– 3 1ImmunOOncology, Pontifical Catholic University of Campinas, Campinas, São Paulo, Brazil; 2UroGen, National Institute of Science, Technology and Innovation in Genitourinary Cancer (INCT), Campinas, São Paulo, Brazil; 3UroScience, State University of Campinas, Campinas, São Paulo, BrazilCorrespondence: Leonardo O Reis, Email reisleo.l@gmail.comBackground: Programmed death-ligand 1 (PD-L1) is a key immune checkpoint molecule involved in tumor immune evasion. Its expression is highly heterogeneous across cancer types and subtypes, influencing therapeutic response. Understanding how different immunomodulatory agents influence PD-L1 expression in breast cancer cells could inform novel therapeutic strategies. This study aimed to investigate the temporal and dose-dependent effects of Bacillus Calmette-Guérin (BCG) and Toll-like receptor (TLR) agonists on PD-L1 expression in two breast cancer cell lines: MCF7 (luminal) and MDA-MB-231 (triple-negative).Methods: MTT (thiazolyl blue tetrazolium bromide) assays were conducted to determine non-cytotoxic concentrations of the immunomodulatory agents: 25 μM IMQ (imiquimod), 10 μg PPG (peptidoglycan), 1 mg LPS (lipopolysaccharide), and two BCG doses (200 μg/mL and 800 μg/mL). Flow cytometry assessed anti-PD-L1 (CD274) antibody expression at 24- and 48 hours post-treatment.Results: In MCF7 cells, BCG induced a dose-dependent upregulation of PD-L1 at 24 hours, which was not sustained at 48 hours, while TLR agonists had minimal or slightly suppressive effects. In contrast, MDA-MB-231 cells exhibited a time-dependent modulation of PD-L1, with an increase at 24 hours followed by a reduction at 48 hours in response to BCG, while TLR agonists consistently decreased PD-L1 levels compared to controls.Conclusion: These findings suggest distinct immunomodulatory responses between cancer subtypes, emphasizing the need for tailored approaches targeting the PD-1/PD-L1 axis. Further studies should explore the molecular mechanisms underlying these differential effects and assess the potential for combinatorial immunotherapeutic strategies in cancer.Keywords: PD-L1, immunomodulation, TLR, BCG, breast cancer |
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| ISSN: | 1178-7074 |