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Neutrophils and TRAIL: insights into BCG immunotherapy for bladder cancer

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Abstract

Bladder cancer is a huge economic burden on the healthcare system and is responsible for approximately 5% of all cancer deaths in humans. Mycobacterium bovis BCG-based therapy is the treatment of choice for superficial bladder cancer. Bacillus Calmette-Guerin (BCG) instillation in the bladder results in a massive local inflammatory response that has secondary antitumor properties. Recent studies have demonstrated that neutrophils present in the bladder after BCG instillation release large amounts of the apoptosis-inducing molecule TRAIL, as well as chemokines that recruit other immune cells, suggesting that neutrophils play a key role in the antitumor response to BCG therapy. This review discusses the impact of these findings on the understanding of the antitumor mechanisms underlying BCG-based immunotherapy for bladder cancer.

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Abbreviations

TNF-related apoptosis-inducing ligand:

TRAIL

Tumor necrosis factor:

TNF

Interferon:

IFN

Polymorphonuclear leukocyte (neutrophil):

PMN

Mycobacterium bovis bacillus Calmette-Guérin:

BCG

Myeloperoxidase:

MPO

Lactoferrin:

LF

Granulocyte-colony stimulating factor:

G-CSF

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Acknowledgments

This work was supported by the University of Iowa Infectious Diseases Postdoctoral Training Grant (MPS), grant AI034879–19 from the National Institutes of Health (WMN), Carver Medical Research Initiative Grant administered through the University of Iowa Carver College of Medicine (TSG), and grant CA109446 from the National Cancer Institute (TSG).

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Authors and Affiliations

  1. Department of Urology, 3204 MERF, University of Iowa, 375 Newton Road, Iowa City, IA, 52242-1089, USA

    Mark P. Simons & Thomas S. Griffith

  2. Inflammation Program, University of Iowa, Iowa City, IA, USA

    Mark P. Simons & William M. Nauseef

  3. Department of Medicine, University of Iowa, Iowa City, IA, USA

    William M. Nauseef

  4. Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, USA

    William M. Nauseef & Thomas S. Griffith

  5. VA Medical Center, Iowa City, IA, USA

    William M. Nauseef

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  1. Mark P. Simons
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Correspondence to Thomas S. Griffith.

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Simons, M.P., Nauseef, W.M. & Griffith, T.S. Neutrophils and TRAIL: insights into BCG immunotherapy for bladder cancer. Immunol Res 39, 79–93 (2007). https://doi.org/10.1007/s12026-007-0084-1

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