Novel Tumor Markers for CTCL Identified

IL-13 has been identified as an autocrine factor for cutaneous T-cell lymphomas (CTCL) and its receptors may be novel tumor markers for the disease, serving as potential therapeutic targets, results of a study published  recently in Blood showed.

“We provide here the first evidence that tumor cells in the skin lesions of CTCL patients produce IL-13 and express IL-13Rα1 and IL-13Rα2,” wrote researchers led by Larisa J. Geskin, MD, of the University of Pittsburgh School of Medicine.

According to the study, previous research has shown that IL-13 promotes growth or survival of certain tumors by acting directly on the tumor, or by acting through suppression of immunosurveillance; however, additional research has shown that IL-13 can also inhibit tumor cell growth.

In this research, Geskin and colleagues sought to examine the role of IL-13 in CTCLs. The researchers used skin and blood samples from 32 patients who had a confirmed diagnosis of CTCL, including 24 who had mycosis fungoides (MF) and 8 who had Sezary syndrome (SS). All of the included patients had elevated CD4⁺ cells in their blood and loss of CD26 expression on CD4⁺ cells.

First, the researchers used conventional immunohistochemistry to compare the skin lesions of patients with CTCL to those of patients with normal skin, atopic dermatitis, and psoriasis. No IL-13 expression was found in normal skin or psoriasis, but was found in atopic dermatitis.

“In CTCL skin biopsies, IL-13 protein was detected in mononuclear cells associated with malignant cell aggregates,” the researchers wrote. “The amount of malignant infiltrate ranged from paucicellular in early stage disease and in SS to florid malignant infiltration of the skin by the tumor-forming aggregates in Stage IIB.”

IL-13 immunopositivity was found to correlate with disease progression (P < .01). The percentage of IL-13 cells increased from about 11% in stages IA and IB disease to about 55% in stage IVA disease. Multicolor immunofluorescence analysis of CTCL skin biopsies stained for IL-13 and tumor markers showed that IL-13 was expressed by inflammatory cells in the tumor microenvironment, as well as by the tumor cells themselves.

“Furthermore, we demonstrate activation of the IL-13 signaling pathway in the skin and blood of CTCL patients and that the addition of IL-13 neutralizing antibodies or soluble IL-13Rα2 to Sezary cell cultures inhibit tumor cell proliferation, implicating IL- 13 as an autocrine factor for the tumor,” the researchers wrote.

Based on these findings, Geskin and colleagues concluded that IL-13 and its receptors are novel tumor markers for CTCL and critical factors in the disease’s etiology.