Cutaneous T-cell lymphoma (CTCL) is a malignancy of skin-trafficking CD4+ T-cells. There presently is no marker that has been identified as being uniquely expressed on the malignant T-cells in CTCL. Therefore, the early diagnosis, as well as the ability to carefully follow the clinical course in response to treatment, can be compromised by the inability to precisely distinguish the malignant cells from normal infiltrating and/or circulating CD4+ T-cells. Our preliminary studies utilizing assays of gene expression, QPCR and flow cytometry have permitted our group to identify a marker, CD164, that, although expressed on some non- lymphocytic tissues, may be uniquely expressed on the malignant T-cells of CTCL patients while not being expressed on the non-malignant T-cells of CTCL patients, nor on the T-cells of healthy volunteers or patients with other skin inflammatory disorders including atopic dermatitis. In this proposal, using a robust number of patient samples, we plan to confirm that CD164 is expressed on the malignant CD4+ T-cells and not on normal T-cells, both in the skin and the blood, and that expression is highly correlated with, and is in fact superior to, the current """"""""state of the art"""""""" methods for distinguishing the malignant T-cells. The use of such a marker would permit both the early diagnosis of disease and would enhance the ability to monitor response to therapy. Importantly, it could also serve as a future therapeutic target. This work will be applied to one of the largest populations of CTCL patients in the U.S. that are evaluated in the Penn Cutaneous Lymphoma Program.

Public Health Relevance

There is no unique marker, which permits the precise distinction between the malignant T-cells of patients with the cutaneous T-cells lymphoma (CTCL) and normal T-cells. In this study we plan to confirm that the cell marker CD164 is uniquely observed to be expressed on the malignant T-cells of patients with CTCL but not on healthy T-cells or lymphocytes of CTCL patients, healthy volunteers or on the T-cells of patients with inflammatory disorders. These findings would likely facilitate the early diagnosis of CTCL, the monitoring of response to therapy and, importantly, CD164 may serve as a target for therapy directed at the tumor cells.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZCA1-RPRB-O (M1))
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Jessup, John M
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University of Pennsylvania
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Benoit, Bernice M; Jariwala, Neha; O'Connor, Geraldine et al. (2017) 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
Rook, Alain H; Gelfand, Joel M; Gelfand, Joel C et al. (2015) Topical resiquimod can induce disease regression and enhance T-cell effector functions in cutaneous T-cell lymphoma. Blood 126:1452-61
Huen, Auris O; Rook, Alain H (2014) Toll receptor agonist therapy of skin cancer and cutaneous T-cell lymphoma. Curr Opin Oncol 26:237-44