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

Nature Reviews. Urology
Jelmer H van PuffelenSita H Vermeulen

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 cou...Continue Reading

Associated Clinical Trials

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Citations

Dec 3, 2020·Urologic Oncology·John P SfakianosAmir Horowitz
Mar 7, 2021·Journal of Clinical Medicine·Renate PichlerMartin Thurnher
Mar 13, 2021·Clinical & Translational Immunology·Vera P MouritsLeo Ab Joosten
May 20, 2021·Nature Reviews. Clinical Oncology·Ignacio MeleroAurelien Marabelle
May 28, 2021·Urology Case Reports·A EguibarS Fernandez
Jun 17, 2021·Nature Reviews. Urology·Niyati LoboAshish M Kamat
Mar 24, 2021·Archivio italiano di urologia, andrologia : organo ufficiale [di] Società italiana di ecografia urologica e nefrologica·Sabrina TrigoAhmed Kotb
Jul 25, 2021·Vaccine·Jonathan HechtBarbara Wegiel

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Methods Mentioned

BETA
blood drawn
biopsy

Clinical Trials Mentioned

NCT03091660

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