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

• Published in: Oncoimmunology Vol. 9; no. 1; p. 1751561
• Main Authors: Blümel, Edda, Munir Ahmad, Shamaila, Nastasi, Claudia, Willerslev-Olsen, Andreas, Gluud, Maria, Fredholm, Simon, Hu, Tengpeng, Surewaard, Bas G J, Lindahl, Lise M, Fogh, Hanne, Koralov, Sergei B, Rahbek Gjerdrum, Lise Mette, Clark, Rachael A, Iversen, Lars, Krejsgaard, Thorbjørn, Bonefeld, Charlotte Menné, Geisler, Carsten, Becker, Jürgen C, Woetmann, Anders, Andersen, Mads Hald, Buus, Terkild Brink, Ødum, Niels
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2020; Taylor & Francis Group
• Subjects: alpha-toxin; Brief Report; cd8+ t cells; ctcl; cytotoxicity; staphylococcus aureus; CD8+ T cells; CTCL; Alpha-toxin; Staphylococcus aureus; cytotoxicity
• ISSN: 2162-4011; 2162-402X; 2162-402X
• DOI: 10.1080/2162402X.2020.1751561

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 by inhibiting CD8 T cell cytotoxicity. Thus, we propose a novel mechanism by which colonization with may contribute to cancer immune evasion and disease progression in CTCL.