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CD164 identifies CD4+ T cells highly expressing genes associated with malignancy in Sézary syndrome: the Sézary signature genes, FCRL3, Tox, and miR-214

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Abstract

Sézary syndrome (SS), a leukemic variant of cutaneous T-cell lymphoma (CTCL), is associated with a significantly shorter life expectancy compared to skin-restricted mycosis fungoides. Early diagnosis of SS is, therefore, key to achieving enhanced therapeutic responses. However, the lack of a biomarker(s) highly specific for malignant CD4+ T cells in SS patients has been a serious obstacle in making an early diagnosis. We recently demonstrated the high expression of CD164 on CD4+ T cells from Sézary syndrome patients with a wide range of circulating tumor burdens. To further characterize CD164 as a potential biomarker for malignant CD4+ T cells, CD164+ and CD164−CD4+ T cells isolated from patients with high-circulating tumor burden, B2 stage, and medium/low tumor burden, B1–B0 stage, were assessed for the expression of genes reported to differentiate SS from normal controls, and associated with malignancy and poor prognosis. The expression of Sézary signature genes: T plastin, GATA-3, along with FCRL3, Tox, and miR-214, was significantly higher, whereas STAT-4 was lower, in CD164+ compared with CD164−CD4+ T cells. While Tox was highly expressed in both B2 and B1–B0 patients, the expression of Sézary signature genes, FCRL3, and miR-214 was associated predominantly with advanced B2 disease. High expression of CD164 mRNA and protein was also detected in skin from CTCL patients. CD164 was co-expressed with KIR3DL2 on circulating CD4+ T cells from high tumor burden SS patients, further providing strong support for CD164 as a disease relevant surface biomarker.

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Acknowledgments

This work was supported by the National Institute of Cancer, R21CA178424 to M.W and A.H.R., Translational Research Grant from the Leukemia and Lymphoma Society to A.H.R, National Institute of Arthritis and Musculoskeletal and Skin Diseases, K23-AR68433 to J.T., and K08-AR065577-03 to B.S.K., American Skin Association Research Grant to B.S.K., and in part by the Intramural Research Program of the National Cancer Institute to D.McV.

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Authors and Affiliations

  1. Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, 421 Curie Blvd, 1049 BRB, Philadelphia, PA, 19104, USA

    Bernice M. Benoit, Neha Jariwala, Adrienne Werth, Lisa Zhu, Christopher Miller, Junko Takeshita, Alain H. Rook & Maria Wysocka

  2. National Cancer Institute, Cancer and Inflammation Program, Frederick, MD, USA

    Geraldine O’Connor & Daniel W. McVicar

  3. Division of Dermatology, Department of Medicine, Washington University, St. Louis, MO, USA

    Landon K. Oetjen, Timothy M. Whelan & Brian S. Kim

  4. Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Andrea B. Troxel

  5. Innate Pharma, Research and Drug Development, Marseille, France

    Hélène Sicard

  6. Department of Anesthesiology, Washington University, St. Louis, MO, USA

    Brian S. Kim

  7. Department of Pathology and Immunology, Washington University, St. Louis, MO, USA

    Brian S. Kim

  8. The Division of Biology and Biomedical Sciences, Washington University, St. Louis, MO, USA

    Landon K. Oetjen & Brian S. Kim

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  1. Bernice M. Benoit
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  2. Neha Jariwala
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Correspondence to Maria Wysocka.

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This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

Dr. Helene Sicard is employed by Innate Pharma, Marseille, France. The authors state no conflict of interest.

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Benoit, B.M., Jariwala, N., O’Connor, G. et al. CD164 identifies CD4+ T cells highly expressing genes associated with malignancy in Sézary syndrome: the Sézary signature genes, FCRL3, Tox, and miR-214. Arch Dermatol Res 309, 11–19 (2017). https://doi.org/10.1007/s00403-016-1698-8

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