Progression of mycosis fungoides occurs through divergence of tumor immunophenotype by differential expression of HLA-DR.

Murray, Duncan and McMurray, Jack Luke and Eldershaw, Suzy and Pearce, Hayden and Davies, Nathaniel and Scarisbrick, Julia J and Moss, Paul (2019) Progression of mycosis fungoides occurs through divergence of tumor immunophenotype by differential expression of HLA-DR. Blood advances, 3 (4). pp. 519-530. ISSN 2473-9537. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs.

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Official URL: http://www.bloodadvances.org/content/3/4/519

Abstract

Immunotherapy is a valuable treatment for many cancer patients, and there is considerable interest in understanding the mechanisms of immune evasion to guide appropriate management. Mycosis fungoides (MF) is a malignant disorder of skin-homing CD4 T cells, and it exhibits a highly variable clinical course during which the tumor-specific immune response may be an important determinant. An unusual feature of MF is that tumor-infiltrating lymphocytes (TILs) must attempt to control a malignant cell from within their own lineage. We obtained skin biopsies and blood from 43 patients with CD4 MF and undertook a detailed phenotypic and functional analysis of CD4 and CD8 T cells. Clonotypic TCRBV staining allowed delineation of malignant and reactive CD4 subsets. CD4 and CD8 TILs displayed a comparable "exhausted" phenotype that was characterized by expression of PD-1 and TIGIT but retained cytotoxic activity and production of interferon-γ and interleukin-17 in early-stage disease. In contrast, tumor cells were much more heterogeneous and were divided into 3 discrete subsets based on differential expression of HLA-DR: "cold" (DR), "exhausted" (DR PD-1), and "evasive" (DR PD-L1) phenotypes. Disease progression was associated with increasing divergence of the tumor phenotype away from that of TILs and reduced functional activity within TILs. These observations reveal that the phenotype and function of TIL populations are constrained at all stages of disease, whereas the tumor evolves discrete phenotypic profiles of escape during clinical progression. The findings should help to direct appropriate immunotherapeutic interventions for individual patients.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs.
Subjects: QW Microbiology. Immunology
Divisions: Ambulatory Care > Dermatology
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Depositing User: Jennifer Manders
Date Deposited: 28 Feb 2019 12:01
Last Modified: 28 Feb 2019 12:01
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/1852

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