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Staphylococcus aureus alpha-toxin inhibits CD8+ T cell-mediated killing of cancer cells in cutaneous T-cell lymphoma

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  • Edda Blümel
  • Shamaila Munir Ahmad
  • Claudia Nastasi
  • Andreas Willerslev-Olsen
  • Maria Gluud
  • Simon Fredholm
  • Tengpeng Hu
  • Bas G J Surewaard
  • Lise M Lindahl
  • Hanne Fogh
  • Sergei B Koralov
  • Lise Mette Rahbek Gjerdrum
  • Rachael A Clark
  • Lars Iversen
  • Thorbjørn Krejsgaard
  • Charlotte Menné Bonefeld
  • Carsten Geisler
  • Jürgen C Becker
  • Anders Woetmann
  • Mads Hald Andersen
  • Terkild Brink Buus
  • Niels Ødum
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Staphylococcus aureus and its toxins have been linked to disease progression and mortality in advanced stages of cutaneous T-cell lymphoma (CTCL). CD8+ T cells play a crucial role in anti-cancer responses and high CD8+ T cell numbers in tumor lesions are associated with a favorable prognosis in CTCL. Here, we show that CD8+ T cells from both healthy donors and Sézary syndrome patients are highly susceptible to cell death induced by Staphylococcal alpha-toxin, whereas malignant T cells are not. Importantly, alpha-toxin almost completely blocks cytotoxic killing of CTCL tumor cells by peptide-specific CD8+ T cells, leading to their escape from induced cell death and continued proliferation. These findings suggest that alpha-toxin may favor the persistence of malignant CTCL cells in vivo by inhibiting CD8+ T cell cytotoxicity. Thus, we propose a novel mechanism by which colonization with Staphylococcus aureus may contribute to cancer immune evasion and disease progression in CTCL.

Original languageEnglish
Article number1751561
JournalOncoImmunology
Volume9
Issue number1
Pages (from-to)1751561
ISSN2162-4011
DOIs
Publication statusPublished - 2020

    Research areas

  • Alpha-toxin, CD8 T cells, CTCL, cytotoxicity, Staphylococcus aureus

ID: 61350348