Differential effects of BCG-Russia and BCG-TICE on trained immunity: Potential implications for bladder cancer immunotherapy
- 1Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada
- 2Department of Pathology and Molecular Medicine, Queen’s University, Kingston, Ontario, Canada
- 3Department of Urology, Queen’s University, Kingston, Ontario, Canada
Abstract
In recent years, immunotherapy of patients with higher-risk non-muscle invasive bladder cancer (NMIBC) in North America has relied on the use of the TICE strain of BCG. However, limitations in the supply chain have warranted investigation of the therapeutic benefit of other strains of BCG, such as BCG-Russia. Trained immunity, a form of innate immune memory, is now widely believed to be an important component of the therapeutic benefit of BCG. Therefore, in the present study we compared the effects of BCG-TICE and BCG-Russia on the acquisition of trained immunity and related secondary immune responses. C57BL/6 mice received a single intravenous injection of BCG-Russia or BCG-TICE. Four weeks later, bone marrow was collected for flow cytometric analysis of hematopoietic stem and progenitor cell (HSPC) populations, generation of bone marrow-derived macrophages, functional assessment of trained immunity, and transcriptomic profiling. Compared with BCG-Russia, BCG-TICE elicited increased levels of trained immunity, characterized by higher production of several proinflammatory cytokines upon secondary activation. BCG promoted the expansion of HSPCs independent of strain. BCG-TICE was linked to upregulation of key inflammation-related genes and enrichment of functionally relevant pathways. The results of this study reveal strain-dependent differences in the ability of BCG to induce innate immune memory and inflammatory pathways that could ultimately determine efficacy of immunotherapy of patients with NMIBC.
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BibTeX
@article{nauman2026differential,
title = {{Differential effects of BCG-Russia and BCG-TICE on trained immunity: Potential implications for bladder cancer immunotherapy}},
author = {Richard W. Nauman and Peter A. Greer and Andrew W. Craig and Tiziana Cotechini and D. Robert Siemens and Charles H. Graham},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0357950},
url = {https://doi.org/10.1371/journal.pone.0357950},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Differential effects of BCG-Russia and BCG-TICE on trained immunity: Potential implications for bladder cancer immunotherapy
AU - Richard W. Nauman
AU - Peter A. Greer
AU - Andrew W. Craig
AU - Tiziana Cotechini
AU - D. Robert Siemens
AU - Charles H. Graham
PY - 2026
DA - 2026/09/11
JO - PLOS One
DO - 10.1371/journal.pone.0357950
UR - https://doi.org/10.1371/journal.pone.0357950
AB - In recent years, immunotherapy of patients with higher-risk non-muscle invasive bladder cancer (NMIBC) in North America has relied on the use of the TICE strain of BCG. However, limitations in the supply chain have warranted investigation of the therapeutic benefit of other strains of BCG, such as BCG-Russia. Trained immunity, a form of innate immune memory, is now widely believed to be an important component of the therapeutic benefit of BCG. Therefore, in the present study we compared the effects of BCG-TICE and BCG-Russia on the acquisition of trained immunity and related secondary immune responses. C57BL/6 mice received a single intravenous injection of BCG-Russia or BCG-TICE. Four weeks later, bone marrow was collected for flow cytometric analysis of hematopoietic stem and progenitor cell (HSPC) populations, generation of bone marrow-derived macrophages, functional assessment of trained immunity, and transcriptomic profiling. Compared with BCG-Russia, BCG-TICE elicited increased levels of trained immunity, characterized by higher production of several proinflammatory cytokines upon secondary activation. BCG promoted the expansion of HSPCs independent of strain. BCG-TICE was linked to upregulation of key inflammation-related genes and enrichment of functionally relevant pathways. The results of this study reveal strain-dependent differences in the ability of BCG to induce innate immune memory and inflammatory pathways that could ultimately determine efficacy of immunotherapy of patients with NMIBC.
SN - 1932-6203
ER -