Staphylococcus aureus alpha-toxin inhibits CD8+ T cell-mediated killing of cancer cells in cutaneous T-cell lymphoma. (1st January 2020)

• Record Type: Journal Article
• 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
• Is Part Of: Oncoimmunology. Volume 9:Number 1(2020)
• Publication Date: 2020-01-01
• Subjects: Alpha-toxin -- Staphylococcus aureus -- CTCL -- CD8+ T cells -- cytotoxicity; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2020.1751561
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: 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.