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

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 AndersenTerkild 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.

Udgave nummer1
StatusUdgivet - 2020

Bibliografisk note

© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.


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