scRNA-Seq reveals anti-lymphoma immune responses in mogamulizumab-associated skin eruptions

Sep 24, 2026

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Mogamulizumab is an anti-CCR4 antibody used for relapsed or refractory cutaneous T-cell lymphomas, but a subset of patients develops mogamulizumab-associated drug rash (MAR), which correlates with improved survival while mechanisms remain unclear. Comprehensive single-cell RNA sequencing of skin from MAR patients was compared with untreated erythrodermic CTCL and healthy controls. Residual malignant clones showed retained CCR4 with decreased SELL/CCR7 and altered immune-silencing and tumor-suppressive programs, while MAR polyclonal T cells exhibited reduced exhaustion markers and increased cytotoxic and anti-cancer features consistent with an anti-lymphoma immune response in the skin microenvironment.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Background

Objectives

Methods

Results

Conclusions

Introduction

Mogamulizumab and MAR background

Histological and diagnostic considerations

Rationale for single-cell RNA sequencing

DOI: 10.1111/jdv.70154 O R I G I N A L A R T I C L E scRNA-Seq reveals anti-lymphoma immune responses inmogamulizumab-associated skin eruptions Shannon Meledathu1 | Agata Kurowski1 | Malini P. Naidu1 | Jonas Adalsteinsson1 | Shane A. Meehan1 | Natalia Alkon2 | Lauren R. Port1 | Sumanth Chennareddy1 | Emry R. Cohenour1 | Grace Christensen1 | Jonah Shulman3 | Nicholas Gulati1 | Constanze Jonak2 | Patrick M. Brunner1 1Icahn School of Medicine at Mount Sinai, New York, New York, USA 2Medical University of Vienna, Vienna, Austria 3Tisch Cancer Institute, Mount Sinai Hospital, New York, New York, USA Correspondence Patrick M. Brunner, Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, NY 10029, USA. [Email:](Email: patrick.brunner@mountsinai.org)[ patrick.brunner@mountsinai.org](Email: patrick.brunner@mountsinai.org) Constanze Jonak, Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Email: [constanze.jonak@meduniwien.ac.at](constanze.jonak@meduniwien.ac.at) Funding information National Center for Advancing Translational Sciences Abstract Background: Mogamulizumab is an anti-CCR4 therapeutic antibody approved for relapsed or refractory mycosis fungoides, Sézary syndrome and adult T-cell leukaemia/lymphoma. During treatment, a subset of patients develops a mogamulizumabassociated drug rash (MAR) that is associated with a better overall survival, but underlying mechanisms remain unclear. In addition, misinterpretation of MAR as cutaneous T-cell lymphoma (CTCL) progression can lead to unnecessary drug discontinuation. Objectives: To conduct a comprehensive molecular characterization of MAR. Methods: We performed single-cell RNA sequencing of skin biopsies from 4 patients with MAR, compared to untreated erythrodermic CTCL (CTCL, n = 6) and healthy control (HC, n = 4) skin. Results: CCR4 was primarily expressed in proliferating and non-proliferating malignant T-cell clones and FOXP3+ regulatory T cells in untreated CTCL, which were significantly decreased in MAR. The few residual malignant clones in MAR showed retained CCR4 expression, but decreases in the central memory markers SELL and CCR7, with upregulation of the MMP2 inhibitor TIMP2 and the tumour suppressor gene RUNX3, consistent with a more silenced immune phenotype. In parallel, polyclonal T cells in MAR lesions exhibited decreases in the exhaustion markers TIGIT and TOX, paralleled by upregulation of markers associated with cytotoxicity (GZMA) and anti-cancer properties (ZNF683). This increase in tumour suppressor and cytotoxicity genes potentially reflects an anti-lymphoma immune response within the MAR skin microenvironment. Conclusions: Our study provides novel insights into the molecular properties of residual malignant clones within MAR that appear silenced, surrounded by a putatively anti-tumor immune response. K E Y W O R D S cutaneous T-cell lymphoma, mogamulizumab, mogamulizumab-associated drug rash, mycosisfungoides, Sezary syndrome, single-cell RNA sequencing | Linked Article: O. E. Akilov. JEur Acad Dermatol Venereol 2026;40:936–937. [https://doi.org/10.1111/jdv.70420](https://doi.org/10.1111/jdv.70420) . | | --- | | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
© 2025 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. | [1078](1078 | wileyonlinelibrary.com/journal/jdv)[ |](1078 | wileyonlinelibrary.com/journal/jdv)[ wileyonlinelibrary.com/journal/jdv](1078 | wileyonlinelibrary.com/journal/jdv) J Eur Acad Dermatol Venereol. 2026;40:1078–1090. INTRODUCTION M

FAQs

What is mogamulizumab and what condition is it used to treat?

Mogamulizumab is an anti-CCR4 therapeutic antibody approved for relapsed or refractory mycosis fungoides, Sézary syndrome, and adult T-cell leukaemia/lymphoma.

Why is MAR clinically important during mogamulizumab treatment?

A subset of patients develops MAR, which is associated with better overall survival. However, MAR can be mistaken for CTCL progression, leading to unnecessary discontinuation of the drug.

What key molecular differences were observed in MAR compared with untreated CTCL?

In MAR, CCR4 expression in residual malignant clones was retained, while markers such as SELL and CCR7 decreased. MAR also showed immune-cell changes including reduced exhaustion markers (TIGIT, TOX) and increased cytotoxicity and anti-cancer-related markers.

Sep 24, 2026

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