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

References

• Willemze R, Cerroni L, Kempf W, Berti E, Facchetti F, Swerdlow SH, Jaffe ES. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019;133(16):1703–8. doi:10.1182/blood-2018-11-881268.
   PubMed Web of Science ®Google Scholar
• Vieyra-Garcia P, Crouch JD, O’Malley JT, Seger EW, Yang CH, Teague JE, Lowry EL. Benign T cells drive clinical skin inflammation in cutaneous T cell lymphoma. JCI Insight. 2019;4(1). doi:10.1172/jci.insight.124233.
   PubMed Web of Science ®Google Scholar
• Litvinov IV, Tetzlaff MT, Thibault P, Gangar P, Moreau L, Watters AK, Provost N. Gene expression analysis in cutaneous T-cell lymphomas (CTCL) highlights disease heterogeneity and potential diagnostic and prognostic indicators. Oncoimmunology. 2017;6(5):e1306618. doi:10.1080/2162402X.2017.1306618.
   PubMed Web of Science ®Google Scholar
• Axelrod PI, Lorber B, Vonderheid EC. Infections complicating mycosis fungoides and Sezary syndrome. JAMA. 1992;267(10):1354–1358. doi:10.1001/jama.1992.03480100060031.
   PubMed Web of Science ®Google Scholar
• Mirvish ED, Pomerantz RG, Geskin LJ. Infectious agents in cutaneous T-cell lymphoma. J Am Acad of Dermatol. 2011;64(2):423–431. doi:10.1016/j.jaad.2009.11.692.
   PubMed Web of Science ®Google Scholar
• Fanok MH, Sun A, Fogli LK, Narendran V, Eckstein M, Kannan K, Dolgalev I. Role of dysregulated cytokine signaling and bacterial triggers in the pathogenesis of cutaneous T-cell lymphoma. J Invest Dermatol. 2018 May;138(5):1116–1125. doi:10.1016/j.jid.2017.10.028.
   PubMed Web of Science ®Google Scholar
• Nguyen V, Huggins RH, Lertsburapa T, Bauer K, Rademaker A, Gerami P, Guitart J. Cutaneous T-cell lymphoma and Staphylococcus aureus colonization. J Am Acad Dermatol. 2008;59(6):949–952. doi:10.1016/j.jaad.2008.08.030.
   PubMed Web of Science ®Google Scholar
• Willerslev-Olsen A, Krejsgaard T, Lindahl LM, Litvinov IV, Fredholm S, Petersen DL, Wasik MA. Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma. Blood. 2016;127(10):1287–1296. doi:10.1182/blood-2015-08-662353.
   PubMed Web of Science ®Google Scholar
• Lindahl LM, Fredholm S, Joseph C, Nielsen BS, Jønson L, Willerslev-Olsen A, Hu T. STAT5 induces miR-21 expression in cutaneous T cell lymphoma. Oncotarget. 2016;7(29):45730–45744. doi:10.18632/oncotarget.10160.
   PubMedGoogle Scholar
• Krejsgaard T, Willerslev-Olsen A, Lindahl LM, Bonefeld CM, Koralov SB, Geisler C, Woetmann A. Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation. Blood. 2014;124(5):761–770. doi:10.1182/blood-2014-01-551184.
   PubMed Web of Science ®Google Scholar
• Nygaard TK, Pallister KB, DuMont AL, DeWald M, Watkins RL, Pallister EQ, Voyich JM. Alpha-toxin induces programmed cell death of human T cells, B cells, and monocytes during USA300 infection. PLoS One. 2012;7(5):e36532. doi:10.1371/journal.pone.0036532.
   PubMed Web of Science ®Google Scholar
• Tkaczyk C, Semenova E, Shi YY, Rosenthal K, Oganesyan V, Warrener P, Sellman BR. Alanine scanning mutagenesis of the MEDI4893 (suvratoxumab) epitope reduces alpha toxin lytic activity in vitro and Staphylococcus aureus fitness in infection models. Antimicrob Agents Chemother. 2018;62(11):e01033–18. doi:10.1128/AAC.01033-18.
   PubMed Web of Science ®Google Scholar
• Hua L, Hilliard JJ, Shi Y, Tkaczyk C, Cheng LI, Yu X, Keller A. Assessment of an anti-alpha-toxin monoclonal antibody for prevention and treatment of Staphylococcus aureus-induced pneumonia. Antimicrob Agents Chemother. 2014;58(2):1108–1117. doi:10.1128/AAC.02190-13.
   PubMed Web of Science ®Google Scholar
• Lindahl LM, Willerslev-Olsen A, Gjerdrum LM, Nielsen PR, Blümel E, Rittig AH, Wasik MA. Antibiotics inhibit tumor and disease activity in cutaneous T-cell lymphoma. Blood. 2019;134(13):1072–1083. doi:10.1182/blood.2018888107.
   PubMed Web of Science ®Google Scholar
• Blümel E, Willerslev-Olsen A, Gluud M, Lindahl LM, Fredholm S, Nastasi C, Persson JL. Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in Cutaneous T-cell lymphoma. Oncoimmunology. 2019;8(11):e1641387. doi:10.1080/2162402X.2019.1641387.
   PubMed Web of Science ®Google Scholar
• Hoppe RT, Medeiros LJ, Warnke RA, Wood GS. CD8-positive tumor-infiltrating lymphocytes influence the long-term survival of patients with mycosis fungoides. J Am Acad Dermatol. 1995;32(3):448–453. doi:10.1016/0190-9622(95)90067-5.
   PubMed Web of Science ®Google Scholar
• Berger CL, Wang N, Christensen I, Longley J, Heald P, Edelson RL. The immune response to class I-associated tumor-specific cutaneous T-cell lymphoma antigens. J Invest Dermatol. 1996;107(3):392–397. doi:10.1111/1523-1747.ep12363378.
   PubMed Web of Science ®Google Scholar
• Gantchev J, Martínez Villarreal A, Xie P, Lefrançois P, Gunn S, Netchiporouk E, Sasseville D. The Ectopic Expression of Meiosis Regulatory Genes in Cutaneous T-Cell Lymphomas (CTCL). Front Oncol. 2019 May 31;9:429. doi:10.3389/fonc.2019.00429.
   PubMed Web of Science ®Google Scholar
• Lefrançois P, Xie P, Wang L, Tetzlaff MT, Moreau L, Watters AK, Netchiporouk E. Gene expression profiling and immune cell-type deconvolution highlight robust disease progression and survival markers in multiple cohorts of CTCL patients. Oncoimmunology. 2018;7(8):e1467856. doi:10.1080/2162402X.2018.1467856.
   PubMed Web of Science ®Google Scholar
• Litvinov IV, Netchiporouk E, Cordeiro B, Zargham H, Pehr K, Gilbert M, Zhou Y. Ectopic expression of embryonic stem cell and other developmental genes in cutaneous T-cell lymphoma. Oncoimmunology. 2014;3(11):e970025. doi:10.4161/21624011.2014.970025.
   PubMed Web of Science ®Google Scholar
• Munir S, Andersen GH, Met Ö, Donia M, Frøsig TM, Larsen SK, Andersen MH. HLA-restricted CTL that are specific for the immune checkpoint ligand PD-L1 occur with high frequency in cancer patients. Cancer Res. 2013;73(6):1764–1776. doi:10.1158/0008-5472.CAN-12-3507.
   PubMed Web of Science ®Google Scholar
• Larsen SK, Munir S, Woetmann A, Frøsig TM, Odum N, Svane IM, Andersen MH. Functional characterization of Foxp3-specific spontaneous immune responses. Leukemia. 2013;27(12):2332–2340. doi:10.1038/leu.2013.196.
   PubMed Web of Science ®Google Scholar
• Oelke M, Moehrle U, Chen JL, Behringer D, Cerundolo V, Lindemann A, Mackensen A. Generation and purification of CD8+ melan-A-specific cytotoxic T lymphocytes for adoptive transfer in tumor immunotherapy. Clin Cancer Res. 2000;6:1997–2005.
   PubMed Web of Science ®Google Scholar
• Munir Ahmad S, Martinenaite E, Hansen M, Junker N, Borch TH, Met Ö, Andersen MH. PD-L1 peptide co-stimulation increases immunogenicity of a dendritic cell-based cancer vaccine. Oncoimmunology. 2016;5(8):e1202391. doi:10.1080/2162402X.2016.1202391.
   PubMed Web of Science ®Google Scholar
• Davis TH, Morton CC, Miller-Cassman R, Balk SP, Kadin ME. Hodgkin’s disease, lymphomatoid papulosis, and cutaneous T-cell lymphoma derived from a common T-cell clone. N Engl J Med. 1992;326(17):1115–1122. doi:10.1056/NEJM199204233261704.
   PubMed Web of Science ®Google Scholar
• Netchiporouk E, Gantchev J, Tsang M, Thibault P, Watters AK, Hughes J-DM, Ghazawi FM. Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1+ leukemic cell lines. Oncotarget. 2017;8(56):95981–95998. doi:10.18632/oncotarget.21619.
   PubMedGoogle Scholar
• Buus TB, Willerslev-Olsen A, Fredholm S, Blümel E, Nastasi C, Gluud M, Gniadecki R. Single-cell heterogeneity in Sézary syndrome. Blood Adv. 2018;2(16):2115–2126. doi:10.1182/bloodadvances.2018022608.
   PubMed Web of Science ®Google Scholar
• Kantekure K, Yang Y, Raghunath P, Schaffer A, Woetmann A, Zhang Q, Wasik M. Expression patterns of the immunosuppressive proteins PD-1/CD279 and PD-L1/CD274 at different stages of cutaneous T-cell lymphoma (CTCL)/mycosis fungoides (MF). American J Dermatopath. 2012;34(1):126–128. doi:10.1097/DAD.0b013e31821c35cb.
   PubMed Web of Science ®Google Scholar
• Capriotti E, Vonderheid EC, Thoburn CJ, Wasik MA, Bahler DW, Hess AD. Expression of T-plastin, FoxP3 and other tumor-associated markers by leukemic T-cells of cutaneous T-cell lymphoma. Leuk Lymphoma. 2008;49(6):1190–1201. doi:10.1080/10428190802064917.
   PubMed Web of Science ®Google Scholar
• Kasprzycka M, Zhang Q, Witkiewicz A, Marzec M, Potoczek M, Liu X, Wang HY. γc-signaling cytokines induce a regulatory T cell phenotype in malignant CD4+ T lymphocytes. J Immunol. 2008;181:2506–2512. doi:10.4049/jimmunol.181.4.2506.
   PubMed Web of Science ®Google Scholar
• Vermeer MH, van Doorn R, Dukers D, Bekkenk MW, Meijer CJ, Willemze R. CD8+ T cells in cutaneous T-cell lymphoma: expression of cytotoxic proteins, Fas ligand, and killing inhibitory receptors and their relationship with clinical behavior. J Clin Oncol. 2001;19(23):4322–4329. doi:10.1200/JCO.2001.19.23.4322.
   PubMed Web of Science ®Google Scholar
• Mairpady Shambat S, Haggar A, Vandenesch F, Lina G, van Wamel WJ, Arakere G, Svensson M. Levels of alpha-toxin correlate with distinct phenotypic response profiles of blood mononuclear cells and with agr background of community-associated staphylococcus aureus isolates. PLoS One. 2014;9(8):e106107. doi:10.1371/journal.pone.0106107.
   PubMed Web of Science ®Google Scholar
• Krejsgaard T, Ralfkiaer U, Clasen-Linde E, Eriksen KW, Kopp KL, Bonefeld CM, Geisler C. Malignant cutaneous T-cell lymphoma cells express IL-17 utilizing the Jak3/Stat3 signaling pathway. J Invest Dermatol. 2011;131(6):1331–1338. doi:10.1038/jid.2011.27.
   PubMed Web of Science ®Google Scholar
• Krejsgaard T, Litvinov IV, Wang Y, Xia L, Willerslev-Olsen A, Koralov SB, Kopp KL. Elucidating the role of interleukin-17F in cutaneous T-cell lymphoma. Blood. 2013;122(6):934–950. doi:10.1182/blood-2013-01-480889.
   Web of Science ®Google Scholar
• Litvinov IV, Shtreis A, Kobayashi K, Glassman S, Tsang M, Woetmann A, Sasseville D. Investigating potential exogenous tumor initiating and promoting factors for Cutaneous T-Cell Lymphomas (CTCL), a rare skin malignancy. Oncoimmunology. 2016;5(7):e1175799. doi:10.1080/2162402X.2016.1175799.
   PubMed Web of Science ®Google Scholar
• Miller LS, Cho JS. Immunity against Staphylococcus aureus cutaneous infections. Nat Rev Immunol. 2011;11(8):505–518. doi:10.1038/nri3010.
   PubMed Web of Science ®Google Scholar
• Lauenborg B, Litvinov IV, Zhou Y, Willerslev-Olsen A, Bonefeld CM, Nastasi C, Fredholm S. Malignant T cells activate endothelial cells via IL-17 F. Blood Cancer J. 2017;7(7):e586. doi:10.1038/bcj.2017.64.
   PubMed Web of Science ®Google Scholar
• Kanda N, Koike S, Watanabe S. IL-17 suppresses TNF-alpha-induced CCL27 production through induction of COX-2 in human keratinocytes. J Allergy Clin Immunol. 2005;116(5):1144–1150. doi:10.1016/j.jaci.2005.08.014.
   PubMed Web of Science ®Google Scholar
• Fossiez F, Banchereau J, Murray R, Van Kooten C, Garrone P, Lebecque S. Interleukin-17. Int Rev Immunol. 1998;16(5–6):541–551. doi:10.3109/08830189809043008.
   PubMedGoogle Scholar
• Kopp KL, Kauczok CS, Lauenborg B, Krejsgaard T, Eriksen KW, Zhang Q, Wasik MA. COX-2-dependent PGE(2) acts as a growth factor in mycosis fungoides (MF). Leukemia. 2010;24(6):1179–1185. doi:10.1038/leu.2010.66.
   PubMed Web of Science ®Google Scholar
• Krejsgaard T, Lindahl LM, Mongan NP, Wasik MA, Litvinov IV, Iversen L, Langhoff E. Malignant inflammation in cutaneous T-cell lymphoma-a hostile takeover. Semin Immunopathol. 2017;39(3):269–282. doi:10.1007/s00281-016-0594-9.
   PubMed Web of Science ®Google Scholar
• Seffens A, Herrera A, Tegla C, Buus TB, Hymes KB, Ødum N. STAT3 dysregulation in mature T and NK cell lymphomas. Cancers (Basel). 2019;11(11). doi:10.3390/cancers11111711.
   PubMed Web of Science ®Google Scholar
• Arina A, Corrales L, Bronte V. Enhancing T cell therapy by overcoming the immunosuppressive tumor microenvironment. Semin Immunol. 2016;28(1):54–63. doi:10.1016/j.smim.2016.01.002.
   PubMed Web of Science ®Google Scholar
• McLane LM, Abdel-Hakeem MS, Wherry EJ. CD8 T cell exhaustion during chronic viral infection and cancer. Annu Rev Immunol. 2019;37:457–495. doi:10.1146/annurev-immunol-041015-055318.
   PubMed Web of Science ®Google Scholar
• Kullander J, Forslund O, Dillner J. Staphylococcus aureus and squamous cell carcinoma of the skin. Cancer Epidemiol Biomarkers Prev. 2009;18(2):472–478. doi:10.1158/1055-9965.EPI-08-0905.
   PubMed Web of Science ®Google Scholar
• Blicharz L, Rudnicka L, Samochocki Z. Staphylococcus aureus: an underestimated factor in the pathogenesis of atopic dermatitis? Postepy Dermatol Alergol. 2019;36(1):11–17. doi:10.5114/ada.2019.82821.
   PubMed Web of Science ®Google Scholar