Gene expression profiling and immune cell-type deconvolution highlight robust disease progression and survival markers in multiple cohorts of CTCL patients

References

• Lamberg SI, Bunn PA, Jr. Cutaneous T-cell lymphomas. Summary of the Mycosis Fungoides Cooperative Group-National Cancer Institute Workshop. Arch Dermatol. 1979;115(9):1103–5. Epub 1979/09/01. doi:10.1001/archderm.1979.04010090053026. PMID:39515.
   PubMedGoogle Scholar
• Han T, Abdel-Motal UM, Chang DK, Sui J, Muvaffak A, Campbell J, Zhu Q, Kupper TS, Marasco WA. Human anti-CCR4 minibody gene transfer for the treatment of cutaneous T-cell lymphoma. PloS one. 2012;7(9):e44455. doi:10.1371/journal.pone.0044455. PMID:22973452.
   PubMed Web of Science ®Google Scholar
• Saunes M, Nilsen TI, Johannesen TB. Incidence of primary cutaneous T-cell lymphoma in Norway. Br J Dermatol. 2009;160(2):376–9. Epub 2008/09/24. doi:10.1111/j.1365-2133.2008.08852.x. PMID:18808419.
   PubMed Web of Science ®Google Scholar
• Ghazawi FM, Netchiporouk E, Rahme E, Tsang M, Moreau L, Glassman S, Provost N, Gilbert M, Jean SE, Pehr K, et al. Comprehensive analysis of cutaneous T-cell lymphoma (CTCL) incidence and mortality in Canada reveals changing trends and geographic clustering for this malignancy. Cancer. 2017;123(18):3550–67. doi:10.1002/cncr.30758. PMID:28493286.
   PubMed Web of Science ®Google Scholar
• Litvinov IV, Tetzlaff MT, Rahme E, Habel Y, Risser DR, Gangar P, Jennings MA, Pehr K, Prieto VG, Sasseville D, et al. Identification of geographic clustering and regions spared by cutaneous T-cell lymphoma in Texas using 2 distinct cancer registries. Cancer. 2015;121(12):1993–2003. doi:10.1002/cncr.29301. PMID:25728286.
   PubMed Web of Science ®Google Scholar
• Litvinov IV, Tetzlaff MT, Rahme E, Jennings MA, Risser DR, Gangar P, Netchiporouk E, Moreau L, Prieto VG, Sasseville D, et al. Demographic patterns of cutaneous T-cell lymphoma incidence in Texas based on two different cancer registries. Cancer Med. 2015;4(9):1440–7. doi:10.1002/cam4.472. PMID:26136403.
   PubMed Web of Science ®Google Scholar
• Ghazawi FM, Netchiporouk E, Rahme E, Tsang M, Moreau L, Glassman S, Provost N, Gilbert M, Jean SE, Roshdy O, et al. Distribution and clustering of cutaneous T-cell lymphoma (CTCL) cases in Canada during 1992 to 2010. J Cutan Med Surg. 2017:1203475417745825. doi:10.1177/1203475417745825. PMID:29241349.
   PubMed Web of Science ®Google Scholar
• Talpur R, Singh L, Daulat S, Liu P, Seyfer S, Trynosky T, Wei W, Duvic M. Long-term outcomes of 1,263 patients with mycosis fungoides and Sezary syndrome from 1982 to 2009. Clin Cancer Res. 2012;18(18):5051–60. doi:10.1158/1078-0432.CCR-12-0604. PMID:22850569.
   PubMed Web of Science ®Google Scholar
• Litvinov IV, Netchiporouk E, Cordeiro B, Dore MA, Moreau L, Pehr K, Gilbert M, Zhou Y, Sasseville D, Kupper TS. The use of transcriptional profiling to improve personalized diagnosis and management of cutaneous T-cell lymphoma (CTCL). Clin Cancer Res. 2015;21(12):2820–9. doi:10.1158/1078-0432.CCR-14-3322. PMID:25779945.
   PubMed Web of Science ®Google Scholar
• Kirsch IR, Watanabe R, O'Malley JT, Williamson DW, Scott LL, Elco CP, Teague JE, Gehad A, Lowry EL, LeBoeuf NR, et al. TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL. Sci Transl Med. 2015;7(308):308ra158. doi:10.1126/scitranslmed.aaa9122. PMID:26446955.
   PubMed Web of Science ®Google Scholar
• Weed J, Girardi M. The difficult–and often delayed–diagnosis of CTCL. Sci Transl Med. 2015;7(308):308fs41. doi:10.1126/scitranslmed.aad2518. PMID:26446952.
   PubMed Web of Science ®Google Scholar
• Talpur R, Sui D, Gangar P, Dabaja BS, Duvic M. Retrospective analysis of prognostic factors in 187 cases of transformed mycosis fungoides. Clinical Lymphoma, Myeloma Leuk. 2016;16(1):49–56. doi:10.1016/j.clml.2015.11.010. PMID:26702474.
   PubMed Web of Science ®Google Scholar
• Sandoval J, Diaz-Lagares A, Salgado R, Servitje O, Climent F, Ortiz-Romero PL, Pérez-Ferriols A, Garcia-Muret MP, Estrach T, Garcia M, et al. MicroRNA expression profiling and DNA methylation signature for deregulated microRNA in cutaneous T-cell lymphoma. J Invest Dermatol. 2015;135(4):1128–37. doi:10.1038/jid.2014.487. PMID:25405321.
   PubMed Web of Science ®Google Scholar
• Ralfkiaer U, Hagedorn PH, Bangsgaard N, Lovendorf MB, Ahler CB, Svensson L, Kopp KL, Vennegaard MT, Lauenborg B, Zibert JR, et al. Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL). Blood. 2011;118(22):5891–900. doi:10.1182/blood-2011-06-358382. PMID:21865341.
   PubMed Web of Science ®Google Scholar
• Kamstrup MR, Gjerdrum LM, Biskup E, Lauenborg BT, Ralfkiaer E, Woetmann A, Ødum N, Gniadecki R. Notch1 as a potential therapeutic target in cutaneous T-cell lymphoma. Blood. 2010;116(14):2504–12. Epub 2010/06/12. doi:10.1182/blood-2009-12-260216. PMID:20538790.
   PubMed Web of Science ®Google Scholar
• Litvinov IV, Cordeiro B, Huang Y, Zargham H, Pehr K, Dore MA, Gilbert M, Zhou Y, Kupper TS, Sasseville D. Ectopic expression of cancer-testis antigens in cutaneous T-cell lymphoma patients. Clin Cancer Res. 2014;20(14):3799–808. Epub 2014/05/23. doi:10.1158/1078-0432.CCR-14-0307. PMID:24850846.
   PubMed Web of Science ®Google Scholar
• Litvinov IV, Netchiporouk E, Cordeiro B, Zargham H, Pehr K, Gilbert M, Zhou Y, Moreau L, Woetmann A, Ødum N, et al. 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. PMID:25941598.
   PubMed Web of Science ®Google Scholar
• Litvinov IV, Tetzlaff MT, Thibault P, Gangar P, Moreau L, Watters AK, Netchiporouk E, Pehr K, Prieto VG, Rahme E, et al. 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
• Litvinov IV, Zhou Y, Kupper TS, Sasseville D. Loss of BCL7A expression correlates with poor disease prognosis in patients with early-stage cutaneous T-cell lymphoma. Leuk Lymphoma. 2012;54(3):653–4. Epub 2012/08/04. doi:10.3109/10428194.2012.717695. PMID:22856870.
   PubMed Web of Science ®Google Scholar
• Litvinov IV, Zhou Y, Pehr K, Kupper TS, Sasseville D. Gene expression analysis in CTCL patients validates the clinical importance of novel oncogenes and tumor suppressor genes. J Invest Dermatol. 2013;133:S62–S. PMID:WOS:000317698900361.
   PubMed Web of Science ®Google Scholar
• Lindahl LM, Besenbacher S, Rittig AH, Celis P, Willerslev-Olsen A, Gjerdrum LMR, Krejsgaard T, Johansen C, Litman T, Woetmann A, et al. Prognostic miRNA classifier in early-stage mycosis fungoides: development and validation in a Danish nationwide study. Blood. 2018;131(7):759–70. Epub 2017/12/07. doi:10.1182/blood-2017-06-788950. PMID:29208599.
   PubMed Web of Science ®Google Scholar
• Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W, Kim D, Nair VS, Xu Y, Khuong A, Hoang CD, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med. 2015;21(8):938–45. Epub 2015/07/21. doi:10.1038/nm.3909. PMID:26193342.
   PubMed Web of Science ®Google Scholar
• Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, Hoang CD, Diehn M, Alizadeh AA. Robust enumeration of cell subsets from tissue expression profiles. Nature methods. 2015;12(5):453–7. Epub 2015/03/31. doi:10.1038/nmeth.3337. PMID:25822800.
   PubMed Web of Science ®Google Scholar
• Litvinov IV, Tetzlaff MT, Thibault P, Gangar P, Moreau L, Watters AK, Netchiporouk E, Pehr K, Prieto VG, Rahme E, et al. 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. PMID:28638728.
   PubMed Web of Science ®Google Scholar
• Lefrançois P, Tetzlaff MT, Moreau L, Watters AK, Netchiporouk E, Provost N, Gilbert M, Ni X, Sasseville D, Duvic M, et al. TruSeq-Based gene expression analysis of formalin-fixed paraffin-embedded (FFPE) cutaneous T-cell lymphoma samples: subgroup analysis results and elucidation of biases from FFPE sample processing on the TruSeq platform. Front Med. 2017;4:153. doi:10.3389/fmed.2017.00153.
   Web of Science ®Google Scholar
• Ungewickell A, Bhaduri A, Rios E, Reuter J, Lee CS, Mah A, Zehnder A, Ohgami R, Kulkarni S, Armstrong R, et al. Genomic analysis of mycosis fungoides and Sezary syndrome identifies recurrent alterations in TNFR2. Nat Genet. 2015;47(9):1056–60. doi:10.1038/ng.3370. PMID:26258847.
   PubMed Web of Science ®Google Scholar
• Choi J, Goh G, Walradt T, Hong BS, Bunick CG, Chen K, Bjornson RD, Maman Y, Wang T, Tordoff J, et al. Genomic landscape of cutaneous T cell lymphoma. Nat Genet. 2015;47(9):1011–9. Epub 2015/07/21. doi:10.1038/ng.3356. PMID:26192916.
   PubMed Web of Science ®Google Scholar
• Wang L, Ni X, Covington KR, Yang BY, Shiu J, Zhang X, Xi L, Meng Q, Langridge T, Drummond J, et al. Genomic profiling of Sezary syndrome identifies alterations of key T cell signaling and differentiation genes. Nat Genet. 2015;47(12):1426–34. doi:10.1038/ng.3444. PMID:26551670.
   PubMed Web of Science ®Google Scholar
• Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B (Methodol). 1995;57(1):289–300.
   Google Scholar
• Shin J, Monti S, Aires DJ, Duvic M, Golub T, Jones DA, Kupper TS. Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome. Blood. 2007;110(8):3015–27. Epub 2007/07/20. blood-2006-12-061507 [pii]. doi:10.1182/blood-2006-12-061507. PMID:17638852.
   PubMed Web of Science ®Google Scholar
• Lee CS, Ungewickell A, Bhaduri A, Qu K, Webster DE, Armstrong R, Weng WK, Aros CJ, Mah A, Chen RO, et al. Transcriptome sequencing in Sezary syndrome identifies Sezary cell and mycosis fungoides-associated lncRNAs and novel transcripts. Blood. 2012;120(16):3288–97. Epub 2012/09/01. doi:10.1182/blood-2012-04-423061. PMID:22936659.
   PubMed Web of Science ®Google Scholar
• Goh WWB, Wang W, Wong L. Why batch effects matter in Omics data, and how to avoid them. Trends Biotechnol. 2017;35(6):498–507. Epub 2017/03/30. doi:10.1016/j.tibtech.2017.02.012. PMID:28351613.
   PubMed Web of Science ®Google Scholar
• Whiteside TL. The tumor microenvironment and its role in promoting tumor growth. Oncogene. 2008;27(45):5904–12. Epub 2008/10/07. doi:10.1038/onc.2008.271. PMID:18836471.
   PubMed Web of Science ®Google Scholar
• Shen-Orr SS, Gaujoux R. Computational deconvolution: extracting cell type-specific information from heterogeneous samples. Curr Opin Immunol. 2013;25(5):571–8. Epub 2013/10/24. doi:10.1016/j.coi.2013.09.015. PMID:24148234.
   PubMed Web of Science ®Google Scholar
• Krejsgaard T, Lindahl LM, Mongan NP, Wasik MA, Litvinov IV, Iversen L, Langhoff E, Woetmann A, Odum N. Malignant inflammation in cutaneous T-cell lymphoma-a hostile takeover. Semin Immunopathol. 2017;39(3):269–82. doi:10.1007/s00281-016-0594-9. PMID:27717961.
   PubMed Web of Science ®Google Scholar
• Ciree A, Michel L, Camilleri-Broet S, Jean Louis F, Oster M, Flageul B, Senet P, Fossiez F, Fridman WH, Bachelez H, et al. Expression and activity of IL-17 in cutaneous T-cell lymphomas (mycosis fungoides and Sezary syndrome). Int J Cancer. 2004;112(1):113–20. doi:10.1002/ijc.20373. PMID:15305382.
   PubMed Web of Science ®Google Scholar
• Krejsgaard T, Litvinov IV, Wang Y, Xia L, Willerslev-Olsen A, Koralov SB, Kopp KL, Bonefeld CM, Wasik MA, Geisler C, et al. Elucidating the role of interleukin-17F in cutaneous T-cell lymphoma. Blood. 2013;122(6):943–50. doi:10.1182/blood-2013-01-480889. PMID:23801634.
   PubMed Web of Science ®Google Scholar
• Bouaziz JD, Ortonne N, Giustiniani J, Schiavon V, Huet D, Bagot M, Bensussan A. Circulating natural killer lymphocytes are potential cytotoxic effectors against autologous malignant cells in sezary syndrome patients. J Invest Dermatol. 2005;125(6):1273–8. Epub 2005/12/16. doi:10.1111/j.0022-202X.2005.23914.x. PMID:16354199.
   PubMed Web of Science ®Google Scholar
• Huang Y, Litvinov IV, Wang Y, Su MW, Tu P, Jiang X, Kupper TS, Dutz JP, Sasseville D, Zhou Y. Thymocyte selection-associated high mobility group box gene (TOX) is aberrantly over-expressed in mycosis fungoides and correlates with poor prognosis. Oncotarget. 2014;5(12):4418–25. doi:10.18632/oncotarget.2031. PMID:24947046.
   PubMedGoogle Scholar
• Huang Y, Su MW, Jiang X, Zhou Y. Evidence of an oncogenic role of aberrant TOX activation in cutaneous T-cell lymphoma. Blood. 2015;125(9):1435–43. doi:10.1182/blood-2014-05-571778. PMID:25548321.
   PubMed Web of Science ®Google Scholar
• Hristov AC, Vonderheid EC, Borowitz MJ. Simplified flow cytometric assessment in mycosis fungoides and Sezary syndrome. Am J Clin Pathol. 2011;136(6):944–53. Epub 2011/11/19. doi:10.1309/AJCP09OTJOYAVZZK. PMID:22095381.
   PubMed Web of Science ®Google Scholar
• Ishida T, Iida S, Akatsuka Y, Ishii T, Miyazaki M, Komatsu H, Inagaki H, Okada N, Fujita T, Shitara K, et al. The CC chemokine receptor 4 as a novel specific molecular target for immunotherapy in adult T-Cell leukemia/lymphoma. Clin Cancer Res. 2004;10(22):7529–39. Epub 2004/12/01. doi:10.1158/1078-0432.CCR-04-0983. PMID:15569983.
   PubMed Web of Science ®Google Scholar
• Ferenczi K, Fuhlbrigge RC, Pinkus J, Pinkus GS, Kupper TS. Increased CCR4 expression in cutaneous T cell lymphoma. J Invest Dermatol. 2002;119(6):1405–10. Epub 2002/12/18. doi:10.1046/j.1523-1747.2002.19610.x. PMID:12485447.
   PubMed Web of Science ®Google Scholar
• Duvic M, Pinter-Brown LC, Foss FM, Sokol L, Jorgensen JL, Challagundla P, Dwyer KM, Zhang X, Kurman MR, Ballerini R, et al. Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma. Blood. 2015;125(12):1883–9. Epub 2015/01/22. doi:10.1182/blood-2014-09-600924. PMID:25605368.
   PubMed Web of Science ®Google Scholar
• Ni X, Jorgensen JL, Goswami M, Challagundla P, Decker WK, Kim YH, Duvic MA. Reduction of regulatory T cells by Mogamulizumab, a defucosylated anti-CC chemokine receptor 4 antibody, in patients with aggressive/refractory mycosis fungoides and Sezary syndrome. Clin Cancer Res. 2015;21(2):274–85. Epub 2014/11/08. doi:10.1158/1078-0432.CCR-14-0830. PMID:25376389.
   PubMed Web of Science ®Google Scholar
• Xia MQ, Hale G, Lifely MR, Ferguson MA, Campbell D, Packman L, Waldmann H. Structure of the CAMPATH-1 antigen, a glycosylphosphatidylinositol-anchored glycoprotein which is an exceptionally good target for complement lysis. Biochem J. 1993;293(Pt 3):633–40. Epub 1993/08/01. PMID:7688956.
   PubMed Web of Science ®Google Scholar
• Watanabe T, Masuyama J, Sohma Y, Inazawa H, Horie K, Kojima K, Uemura Y, Aoki Y, Kaga S, Minota S, et al. CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells. Clin Immunol. 2006;120(3):247–59. Epub 2006/06/27. doi:10.1016/j.clim.2006.05.006. PMID:16797237.
   PubMed Web of Science ®Google Scholar
• Hahtola S, Tuomela S, Elo L, Hakkinen T, Karenko L, Nedoszytko B, Heikkilä H, Saarialho-Kere U, Roszkiewicz J, Aittokallio T, et al. Th1 response and cytotoxicity genes are down-regulated in cutaneous T-cell lymphoma. Clin Cancer Res. 2006;12(16):4812–21. Epub 2006/08/18. doi:10.1158/1078-0432.CCR-06-0532. PMID:16914566.
   PubMed Web of Science ®Google Scholar
• Lundin J, Hagberg H, Repp R, Cavallin-Stahl E, Freden S, Juliusson G, Rosenblad E, Tjønnfjord G, Wiklund T, Osterborg A. Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. Blood. 2003;101(11):4267–72. Epub 2003/01/25. doi:10.1182/blood-2002-09-2802. PMID:12543862.
   PubMed Web of Science ®Google Scholar
• Kennedy GA, Seymour JF, Wolf M, Januszewicz H, Davison J, McCormack C, Ryan G, Prince HM. Treatment of patients with advanced mycosis fungoides and Sezary syndrome with alemtuzumab. Eur J Haematol. 2003;71(4):250–6. Epub 2003/09/03. doi:10.1034/j.1600-0609.2003.00143.x. PMID:12950233.
   PubMed Web of Science ®Google Scholar
• Ginaldi L, De Martinis M, Matutes E, Farahat N, Morilla R, Dyer MJ, Catovsky D. Levels of expression of CD52 in normal and leukemic B and T cells: correlation with in vivo therapeutic responses to Campath-1H. Leuk Res. 1998;22(2):185–91. Epub 1998/05/21. doi:10.1016/S0145-2126(97)00158-6. PMID:9593475.
   PubMed Web of Science ®Google Scholar
• Sicard H, Bonnafous C, Morel A, Bagot M, Bensussan A, Marie-Cardine A. A novel targeted immunotherapy for CTCL is on its way: anti-KIR3DL2 mAb IPH4102 is potent and safe in non-clinical studies. Oncoimmunology. 2015;4(9):e1022306. Epub 2015/09/26. doi:10.1080/2162402X.2015.1022306. PMID:26405593.
   PubMed Web of Science ®Google Scholar
• Lino-Silva LS, Salcedo-Hernandez RA, Garcia-Perez L, Meneses-Garcia A, Zepeda-Najar C. Basal neutrophil-to-lymphocyte ratio is associated with overall survival in melanoma. Melanoma Res. 2017;27(2):140–4. Epub 2017/01/27. doi:10.1097/CMR.0000000000000333. PMID:28125448.
   PubMed Web of Science ®Google Scholar
• Lauenborg B, Litvinov IV, Zhou Y, Willerslev-Olsen A, Bonefeld CM, Nastasi C, Fredholm S, Lindahl LM, Sasseville D, Geisler C, et al. Malignant T cells activate endothelial cells via IL-17F. Blood Cancer J. 2017;7(7):e586. Epub 2017/07/22. doi:10.1038/bcj.2017.64. PMID:28731459.
   PubMedGoogle Scholar
• Willerslev-Olsen A, Krejsgaard T, Lindahl LM, Litvinov IV, Fredholm S, Petersen DL, Nastasi C, Gniadecki R, Mongan NP, Sasseville D, et al. Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma. Blood. 2016;127(10):1287–96. doi:10.1182/blood-2015-08-662353. PMID:26738536.
   PubMed Web of Science ®Google Scholar
• De A, Raychaudhury T, Rajagopalan M, Sarda A, Sharma N. A case of cutaneous T-cell lymphoma, masquerading as psoriasis, was given etanercept and secukinumab: emphasizing the need for biopsy confirmation before starting biologics. Indian J Dermatol. 2017;62(5):533–5. Epub 2017/10/06. doi:10.4103/ijd.IJD_311_17. PMID:28979022.
   PubMed Web of Science ®Google Scholar
• Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, Zackheim H, Duvic M, Estrach T, Lamberg S, et al. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007;110(6):1713–22. doi:10.1182/blood-2007-03-055749. PMID:17540844.
   PubMed Web of Science ®Google Scholar