@article{Barbosa2026, 
author = {Gabriela R. Barbosa and Luciana S. B. Dal Col and Caroline C. Bighetto and Maria Carolina X. de Godoy and Marina D. B. P. Campioni and Marcus V. Sadi and Alessandra Gambero and Leonardo O. Reis},
title = {BCG Induces PD-1 Upregulation on Circulating CD8+ T Cells and IL-6 and IL-8 Secretion In Vitro},
year = {2026},
journal = {Oncology Research},
volume = {34},
number = {7},
pages = {20},
keywords = {BCG immunotherapy, breast cancer, Toll-like receptors agonists, bladder cancer},
url = {https://www.sciopen.com/article/10.32604/or.2026.075738},
doi = {10.32604/or.2026.075738},
abstract = {BackgroundsBacillus Calmette-Guérin (BCG) remains the most effective adjuvant therapy for non-muscle-invasive bladder cancer (NMIBC); however, the immunological underpinnings of its efficacy remain incompletely understood. This study aims to elucidate the dual immunomodulatory roles of BCG by integrating systemic and tumor-intrinsic analyses, through determining the systemic effects of BCG instillation on immune checkpoint expression and direct inflammatory response in a previously established in vitro tumor model.MethodsWe investigated systemic and tumor-intrinsic immune responses to BCG. Flow cytometry was used to evaluate immune checkpoint expression on circulating lymphocyte subsets in NMIBC patients (n = 7) at various stages of BCG therapy. In parallel, an in vitro model of PD-L1 modulation using breast cancer cell lines (MDA-MB-231 and MCF-7) was stimulated with BCG and TLR agonists, and the secretion of IL-6 and IL-8 was assessed using an ELISA.ResultsPeripheral immune profiling revealed stable lymphocyte frequencies, but a significant increase in PD-1 expression on CD8+ T cells following BCG exposure (p = 0.0068), with no significant modulation in CTLA-4 levels. In vitro, MDA-MB-231 cells exhibited robust IL-6 secretion upon high-dose BCG stimulation (p = 0.0277), whereas MCF-7 cells showed increased IL-8 release (p < 0.0001). Other TLR agonists had limited effects.ConclusionsBCG induces dual immunomodulation, characterized by PD-1 upregulation in systemic CD8+ T cells and the release of pro-inflammatory cytokines from epithelial tumor cells. These findings support the potential of combining BCG with immune checkpoint inhibitors and underscore IL-6 and IL-8 as candidate biomarkers of tumor-intrinsic responsiveness.}
}