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

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...

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Published inOncoimmunology 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
LanguageEnglish
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
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Abstract 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.
AbstractList 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.
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.
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.
Author Koralov, Sergei B
Iversen, Lars
Willerslev-Olsen, Andreas
Bonefeld, Charlotte Menné
Krejsgaard, Thorbjørn
Munir Ahmad, Shamaila
Surewaard, Bas G J
Gluud, Maria
Fredholm, Simon
Woetmann, Anders
Buus, Terkild Brink
Nastasi, Claudia
Andersen, Mads Hald
Ødum, Niels
Hu, Tengpeng
Rahbek Gjerdrum, Lise Mette
Clark, Rachael A
Lindahl, Lise M
Becker, Jürgen C
Blümel, Edda
Fogh, Hanne
Geisler, Carsten
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  organization: Department of Dermatology, Copenhagen University Hospital, Copenhagen, Denmark
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  surname: Koralov
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  organization: Department of Pathology, New York University School of Medicine, New York, USA
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  organization: Department of Pathology, Zealand University Hospital, Roskilde, Denmark
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  organization: Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
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  givenname: Jürgen C
  orcidid: 0000-0001-9183-653X
  surname: Becker
  fullname: Becker, Jürgen C
  organization: Translational Skin Cancer Research, German Cancer Consortium (DKTK), University Hospital Essen and Deutsches Krebsforschungszentrum (DKFZ), Essen, Germany
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  surname: Andersen
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  givenname: Niels
  surname: Ødum
  fullname: Ødum, Niels
  organization: LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
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Issue 1
Keywords CD8+ T cells
CTCL
Alpha-toxin
Staphylococcus aureus
cytotoxicity
Language English
License 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
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Snippet 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...
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...
Staphylococcus aureus and its toxins have been linked to disease progression and mortality in advanced stages of cutaneous T-cell lymphoma (CTCL). CD8 + T...
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SubjectTerms alpha-toxin
Brief Report
cd8+ t cells
ctcl
cytotoxicity
staphylococcus aureus
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Title Staphylococcus aureus alpha-toxin inhibits CD8 + T cell-mediated killing of cancer cells in cutaneous T-cell lymphoma
URI https://www.ncbi.nlm.nih.gov/pubmed/32363124
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