Monitoring Malignant T-Cell Clones by Direct TCR Expression Assay in Patients With Leukemic Cutaneous T-Cell Lymphoma During Extracorporeal Photopheresis

Authors

Xiao Ni
Sourindra Maiti
Alissa Redko
Pedram Bijani
Madeleine Duvic

Publication Date

3-1-2022

Journal

Photodermatology, Photoimmunology & Photomedicine

Abstract

Background/purpose: Accurate assessment of malignant T-cell clones in patients with leukemic cutaneous T-cell lymphoma (L-CTCL) is crucial for diagnosis, treatment, and monitoring disease. Although multiple approaches to quantitate malignant T-cell clones have been reported, a cost-effective assay with broad coverage is not available. We report a NanoString-nCounter-Technology-based direct TCR expression assay (DTEA) that was previously developed to quantify both TCR-Vα and TCR-Vβ usages after adoptive immunotherapy. This study was performed to test the effectiveness of DTEA in assessing malignant T-cell clones in L-CTCL patients.

Methods: Total RNAs extracted from peripheral blood mononuclear cells of patients before starting extracorporeal photopheresis (ECP) (n = 15) and during therapy at 3 months and 6 months (n = 12) were used for DTEA, with customized probes for 45 TCR-Vα and 46 TCR-Vβ family members.

Results: At baseline, DTEA detected TCR-Vβ clones in all 15 patients (100%) compared to flow cytometry that detected TCR-Vβ clones in 9 of 13 patients (69.2%). In addition to predominant TCR-Vβ clones, DTEA also detected additional TCR-Vβ clones in 8 of 15 patients (53.3%). Furthermore, DTEA simultaneously identified clonal TCR-Vα usages, which allowed us to pair TCR-Vα and TCRVβ usages by malignant T-cells and identify diversified clonotypes. Changes in the relative frequencies of clonal TCR-Vβ and TCRVα usages over therapy were consistent with patients' clinical responses.

Conclusions: Our results indicate that DTEA can effectively assess malignant T-cell clones by detecting clonal TCR-Vα and TCR-Vβ usages. By providing a global view of TCR repertoires, DTEA may also help us understand the origin(s) of malignant T-cells and pathogenesis of CTCL.

Keywords

Clone Cells, Humans, Leukocytes, Mononuclear, Lymphoma, T-Cell, Cutaneous, Photopheresis, Receptors, Antigen, T-Cell, Skin Neoplasms, T-Lymphocytes, Non-Hodgkin’s lymphoma, Sézary Syndrome, Mycosis Fungoides, T cell receptor, extracorporeal photopheresis

DOI

10.1111/phpp.12732

PMID

34543492

PMCID

PMC11917527

PubMedCentral® Posted Date

9-26-2021

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes