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

Research output: Contribution to journalJournal articlepeer-review

  • Edda Blümel
  • Shamaila Munir Ahmad
  • Claudia Nastasi
  • Andreas Willerslev-Olsen
  • Simon Fredholm
  • Tengpeng Hu
  • Bas G.J. Surewaard
  • Lise M. Lindahl
  • Hanne Fogh
  • Sergei B. Koralov
  • Rachael A. Clark
  • Lars Iversen
  • Thorbjørn Krejsgaard
  • Jürgen C. Becker

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
Number of pages9
ISSN2162-4011
DOIs
Publication statusPublished - 2020

    Research areas

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

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