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Earlier CTCL Diagnosis with TCR Sequencing

doi: 10.1097/01.COT.0000473591.51814.e8

Cutaneous T cell lymphoma (CTCL) is considered difficult to diagnose early in part because the mycosis fungoides that characterize the disease can resemble other skin lesions including such benign conditions as psoriasis and atopic dermatitis. But, researchers have now identified a potentially alternative method for diagnosing CTCL—high-throughput T-cell receptor (TCR) sequencing.

As noted in a study published online ahead of print in Science Translational Medicine (DOI: 10.1126/scitranslmed.aaa9122), the research—“co-first” authors are Ilan R. Kirsch, MD, of Adaptive Biotechnologies in Seattle and Rei Watanabe, MD, PhD, of Brigham and Women's Hospital, Harvard Medical School—showed that high-throughput TCR sequencing accurately diagnosed CTCL in all stages, discriminated CTCL from benign inflammatory skin diseases, and provided insights into the cell of origin and location of malignant CTCL cells in skin.

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Research Details

The team analyzed DNA from biopsies of 46 patients with CTCL skin lesions, 23 patients with psoriasis (with lesional skin), 11 patients with eczematous dermatitis, 12 patients with contact dermatitis, and 12 patients with pityriasis lichenoides et varioliformis acuta (PLEVA), as well as from the skin of six healthy donors using the high-throughput TCR sequencing technique.

By identifying and quantifying malignant T cells, the technique accurately distinguished CTCL from other skin diseases in all 46 patients. In contrast, polymerase chain reaction, the most commonly used diagnostic test for CTCL, correctly diagnosed only 70 percent of the cancer samples, and often missed earlier-stage tumors.

For a subset of patients, the researchers used high-throughput TCR sequencing to track malignant T cells over time, making it possible to detect early recurrence and monitor response to treatment. TCR sequencing also revealed new insights into the cell of origin for CTCL—that the cancer arises from mature, and not immature, T cells, which may help direct the design of more effective therapy, the researchers said.

“Because of its ability to identify and quantify individual T cell clones, high-throughput TCR sequencing is a promising technique to apply to the diagnosis of CTCL,” the authors said. “T cell clones may be frequent within the total T cell population in benign inflammatory skin diseases, but the absolute number of these cells per unit of skin rarely exceeded a certain threshold (about 1:1000).

In contrast, in CTCL clonal T cells accumulated not only in frequency but also in absolute numbers to levels that exceed those observed in benign inflammatory skin diseases.”

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Accompanying Commentary

In an accompanying commentary (STM DOI: 10.1126/scitranslmed.aad2518), Jason Weed and Michael Girardi, MD, both of the Department of Dermatology at Yale School of Medicine, note that high-throughput TCR sequencing could yield many advantages over current techniques for diagnosing CTCL: “The potential utility and advantages of high-throughput TCR sequencing analysis may go beyond early and accurate diagnosis.

“By sequencing and quantifying all rearranged TCRs present in a sample, high-throughput TCR sequencing captures and illuminates the presence of not only malignant T cells but also the local infiltrating lymphocytes (in skin) and the effector/memory and naïve T cells (in blood). Analysis of these nonmalignant T cell populations may one day improve prognostic accuracy by serving as an indicator of the antitumor response and, in later stages of disease, a measure of the compromised immune system's capacity to generate and/or maintain T cell diversity.”

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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