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

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  • Edda Blümel, Københavns Universitet
  • ,
  • Shamaila Munir Ahmad, Københavns Universitet
  • ,
  • Claudia Nastasi, Københavns Universitet
  • ,
  • Andreas Willerslev-Olsen, Københavns Universitet
  • ,
  • Maria Gluud, Københavns Universitet
  • ,
  • Simon Fredholm, Københavns Universitet
  • ,
  • Tengpeng Hu, Københavns Universitet
  • ,
  • Bas G.J. Surewaard, University of Calgary
  • ,
  • Lise M. Lindahl
  • Hanne Fogh, Københavns Universitet
  • ,
  • Sergei B. Koralov, New York University
  • ,
  • Lise Mette Rahbek Gjerdrum, Københavns Universitet
  • ,
  • Rachael A. Clark, Harvard University
  • ,
  • Lars Iversen
  • Thorbjørn Krejsgaard, Københavns Universitet
  • ,
  • Charlotte Menné Bonefeld, Københavns Universitet
  • ,
  • Carsten Geisler, Københavns Universitet
  • ,
  • Jürgen C. Becker, University of Duisburg-Essen
  • ,
  • Anders Woetmann, Københavns Universitet
  • ,
  • Mads Hald Andersen, Center for Cancer Immune Therapy (CCIT), Københavns Universitet
  • ,
  • Terkild Brink Buus, Københavns Universitet
  • ,
  • Niels Ødum, Københavns Universitet

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.

OriginalsprogEngelsk
Artikelnummer1751561
TidsskriftOncoImmunology
Vol/bind9
Nummer1
Antal sider8
ISSN2162-4011
DOI
StatusUdgivet - 2020

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