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van Puffelen JH, Keating ST, Oosterwijk E, et al. Trained immunity as a molecular mechanism for BCG immunotherapy in bladder cancer. Nat Rev Urol. 2020;17(9):513-525doi: 10.1038/s41585-020-0346-4.
van Puffelen, J. H., Keating, S. T., Oosterwijk, E., van der Heijden, A. G., Netea, M. G., Joosten, L. A. B., & Vermeulen, S. H. (2020). Trained immunity as a molecular mechanism for BCG immunotherapy in bladder cancer. Nature reviews. Urology, 17(9), 513-525. https://doi.org/10.1038/s41585-020-0346-4
van Puffelen, Jelmer H, et al. "Trained immunity as a molecular mechanism for BCG immunotherapy in bladder cancer." Nature reviews. Urology vol. 17,9 (2020): 513-525. doi: https://doi.org/10.1038/s41585-020-0346-4
van Puffelen JH, Keating ST, Oosterwijk E, van der Heijden AG, Netea MG, Joosten LAB, Vermeulen SH. Trained immunity as a molecular mechanism for BCG immunotherapy in bladder cancer. Nat Rev Urol. 2020 Sep;17(9):513-525. doi: 10.1038/s41585-020-0346-4. Epub 2020 Jul 16. PMID: 32678343.
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Nat Rev Urol. 2020 Sep;17(9):513-525. doi: 10.1038/s41585-020-0346-4. Epub 2020 Jul 16.

Trained immunity as a molecular mechanism for BCG immunotherapy in bladder cancer.

Nature reviews. Urology

Jelmer H van Puffelen, Samuel T Keating, Egbert Oosterwijk, Antoine G van der Heijden, Mihai G Netea, Leo A B Joosten, Sita H Vermeulen

Affiliations

  1. Department for Health Evidence, Radboud University Medical Center, Radboud Institute for Health Sciences (RIHS), Nijmegen, Netherlands.
  2. Department of Internal Medicine, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, Netherlands.
  3. Department of Urology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences (RIMLS), Nijmegen, Netherlands.
  4. Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
  5. Department of Medical Genetics, Iuliu Ha?ieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
  6. Department for Health Evidence, Radboud University Medical Center, Radboud Institute for Health Sciences (RIHS), Nijmegen, Netherlands. [email protected].

PMID: 32678343 DOI: 10.1038/s41585-020-0346-4

Abstract

Intravesical BCG instillation is the gold-standard adjuvant immunotherapy for patients with high-risk non-muscle-invasive bladder cancer. However, the precise mechanism of action by which BCG asserts its beneficial effects is still unclear. BCG has been shown to induce a non-specific enhancement of the biological function in cells of the innate immune system, creating a de facto heterologous immunological memory that has been termed trained immunity. Trained immunity or innate immune memory enables innate immune cells to mount a more robust response to secondary non-related stimuli after being initially primed (or trained) by a challenge such as BCG. BCG-induced trained immunity is characterized by the metabolic rewiring of monocyte intracellular metabolism and epigenetic modifications, which subsequently lead to functional reprogramming effects, such as an increased production of cytokines, on restimulation. Results from BCG vaccination studies in humans show that trained immunity might at least partly account for the heterologous beneficial effects of BCG vaccination. Additionally, immunity might have a role in the effect of BCG immunotherapy for bladder cancer. Based on these indications, we propose that trained immunity could be one of the important mechanisms mediating BCG immunotherapy and could provide a basis for further improvements towards a personalized approach to BCG therapy in non-muscle-invasive bladder cancer.

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