Novel markers to monitor treatment response and progression in Sézary syndrome

CD39 and CD73 are emerging markers to identify and quantify tumour cells in patients with Sézary syndrome. Various analyses showed that the levels of these molecules may help physicians monitor disease progression and evaluate treatment response to mogamulizumab in the blood.

“Sézary syndrome is a rare and aggressive type of cutaneous T-cell lymphoma,” explained Dr Sara Marchisio (University of Turin, Italy) [1]. “The clinical presentation comprises erythroderma, pruritus, alopecia, onychodystrophy, palmoplantar hyperkeratosis, lymphadenopathy, and atypical CD4-positive T cells (known as Sézary cells) in the skin, lymph nodes, and blood [2].” Patients with this condition have a compromised immune system and have an increased risk of life-threatening infections. According to Dr Marchisio, the 5-year survival rate is approximately 30%. Histological findings in Sézary syndrome are often non-specific, complicating diagnosis. As a result, several diagnostic criteria have been developed, including clinical features such as erythroderma and lymphadenopathy, the identification of T-cell clonality in blood and skin, and the presence of abnormal T-cells in blood. Specific thresholds for the latter involve the presence of more than 1,000 Sézary cells/μL, loss of CD7 and/or CD26 as determined by immunophenotyping, and a CD4/CD8 ratio greater than 10.

Despite these criteria, diagnostic accuracy remains imperfect. “We need studies to improve the detection and quantification of tumour cells by flow cytometry,” suggested Dr Marchisio. Her research team investigated the potential of 3 new markers, namely CD39, CD73, and CD38. These surface proteins are involved in the production of adenosine, a potent immunosuppressive metabolite that can contribute to immune system dysfunction. “A previous study showed that these 3 molecules are aberrantly expressed in circulating CD4-positive T cells in patients with Sézary syndrome,” clarified Dr Marchisio. “Our research question was whether these markers, CD39 and CD73 in particular, could serve as reliable tools to identify and quantify Sézary tumour cells.”

The research group first needed to evaluate whether these markers are expressed in tumour cells. Flow cytometry analysis performed on the cells of patients with Sézary syndrome showed that CD39 and CD73 were exclusively overexpressed on tumour cells. Furthermore, a clear correlation was observed between the percentage of CD39-positive T cells and the percentage of tumour cells in the blood (r=0.81; P=0.0005). “This finding underlines that CD39 can be used as a marker to identify and quantify tumour cells in the blood,” emphasised Dr Marchisio. A subsequent question was raised: how is the CD39 and CD73 expression affected by treatment?

Mogamulizumab, a CCR4 inhibitor, triggers cytotoxic T-cells to target tumour cells. CCR4 can be expressed by different T cells, including Sézary cells. “Most patients have a favourable response to this therapy, particularly in the blood compartment,” mentioned Dr Marchisio. “Unfortunately, the median progression-free survival is only 8 months [3].” This underscores the need for reliable biomarkers to monitor disease status. The analysis showed that CD39 and CD73 levels were significantly reduced following mogamulizumab treatment. In cases where tumour cells recurred, marked increases in CD39 and CD73 were also seen, indicating that these molecules are dynamically modulated in response to treatment.

“These are important findings because they demonstrate that CD39 and CD37 can be used to track the disease,” Dr Marchisio concluded. “In fact, the levels of these markers reflect the patient’s response to mogamulizumab therapy. The next step would be to assess whether these molecules contribute to the immunosuppressive microenvironment that increases the risk of life-threatening infections in patients with Sézary syndrome. Understanding this could pave the way for novel therapeutic strategies.

1. Marchisio S, et al. Evaluation of CD39, CD73, and CD38 as potential biomarkers for monitoring mogamulizumab response in Sézary syndrome. Dermatologendagen 2025, 10–11 April, Apeldoorn, the Netherlands.
2. Chu AC, et al. Blood. 1989;73(6):1603-1607.
3. Latzka J, et al. Eur J Cancer. 2023;195:113343.

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Posted on 5 June 20255 June 2025