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

被引：28

作者：

Blumel, Edda ^{[1
]}

Munir Ahmad, Shamaila ^{[2
]}

Nastasi, Claudia ^{[1
]}

Willerslev-Olsen, Andreas ^{[1
]}

Gluud, Maria ^{[1
]}

Fredholm, Simon ^{[1
]}

Hu, Tengpeng ^{[1
]}

Surewaard, Bas G. J. ^{[3
]}

Lindahl, Lise M. ^{[4
]}

Fogh, Hanne ^{[5
]}

Koralov, Sergei B. ^{[6
]}

Gjerdrum, Lise Mette Rahbek ^{[7
]}

Clark, Rachael A. ^{[8
]}

Iversen, Lars ^{[4
]}

Krejsgaard, Thorbjorn ^{[1
]}

Bonefeld, Charlotte Menne ^{[1
]}

Geisler, Carsten ^{[1
]}

Becker, Jurgen C. ^{[9
,10
]}

Woetmann, Anders ^{[1
]}

Andersen, Mads Hald ^{[2
]}

Buus, Terkild Brink ^{[1
]}

Odum, Niels ^{[1
]}

机构：

[1] Univ Copenhagen, Dept Immunol & Microbiol, Skin Immunol Res Ctr, LEO Fdn, Maersk Tower 07-12-70,Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark

[2] Copenhagen Univ Hosp, Herlev Hosp, Dept Hematol & Oncol, Ctr Canc Immune Therapy CCIT, Herlev, Denmark

[3] Univ Calgary, Snyder Inst Chron Dis, Dept Physiol & Pharmacol, Calgary, AB, Canada

[4] Aarhus Univ Hosp, Dept Dermatol, Aarhus, Denmark

[5] Copenhagen Univ Hosp, Dept Dermatol, Copenhagen, Denmark

[6] NYU, Sch Med, Dept Pathol, New York, NY USA

[7] Zealand Univ Hosp, Dept Pathol, Roskilde, Denmark

[8] Harvard Med Sch, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA

[9] Univ Hosp Essen, German Canc Consortium DKTK, Translat Skin Canc Res, Essen, Germany

[10] Deutsch Krebsforschungszentrum DKFZ, Essen, Germany

来源：

ONCOIMMUNOLOGY | 2020年 / 9卷 / 01期

关键词：

Alpha-toxin; Staphylococcus aureus; CTCL; CD8(+) T cells; cytotoxicity;

D O I：

10.1080/2162402X.2020.1751561

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 Sezary syndrome patients are highly susceptible to cell death induced by Staphylococcal alpha-toxin, whereas malignant T cells are not. Importantly, alphatoxin 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.

引用

页数：8