Staphylococcus aureus alpha-toxin inhibits CD8+ T cell-mediated killing of cancer cells in cutaneous T-cell lymphoma
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Staphylococcus aureus alpha-toxin inhibits CD8+ T cell-mediated killing of cancer cells in cutaneous T-cell lymphoma. / 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.
I: OncoImmunology, Bind 9, Nr. 1, 1751561, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Staphylococcus aureus alpha-toxin inhibits CD8+ T cell-mediated killing of cancer cells in cutaneous T-cell lymphoma
AU - Blümel, Edda
AU - Munir Ahmad, Shamaila
AU - Nastasi, Claudia
AU - Willerslev-Olsen, Andreas
AU - Gluud, Maria
AU - Fredholm, Simon
AU - Hu, Tengpeng
AU - Surewaard, Bas G.J.
AU - Lindahl, Lise M.
AU - Fogh, Hanne
AU - Koralov, Sergei B.
AU - Rahbek Gjerdrum, Lise Mette
AU - Clark, Rachael A.
AU - Iversen, Lars
AU - Krejsgaard, Thorbjørn
AU - Bonefeld, Charlotte Menné
AU - Geisler, Carsten
AU - Becker, Jürgen C.
AU - Woetmann, Anders
AU - Andersen, Mads Hald
AU - Buus, Terkild Brink
AU - Ødum, Niels
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Alpha-toxin
KW - CD8 T cells
KW - CTCL
KW - cytotoxicity
KW - Staphylococcus aureus
U2 - 10.1080/2162402X.2020.1751561
DO - 10.1080/2162402X.2020.1751561
M3 - Journal article
C2 - 32363124
AN - SCOPUS:85083570939
VL - 9
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 1
M1 - 1751561
ER -
ID: 243011886