Successful treatment of mogamulizumab‐resistant mycosis fungoides with mogamulizumab plus etoposide combined therapy: Investigation of the immunomodulatory effects of etoposide on the tumor microenvironment
- 2 May 2020
- journal article
- research article
- Published by Hindawi Limited in Dermatologic Therapy
- Vol. 33 (4), e13487
- https://doi.org/10.1111/dth.13487
Abstract
Mogamulizumab shows cytotoxicity against CCR4+ lymphoma cells by antibody‐dependent cell‐mediated cytotoxicity (ADCC) in advanced cutaneous T cell lymphoma (CTCL) patients. Although mogamulizumab is used as one of the anchor drugsfor the treatment of advanced CTCL, its efficacy is unsatisfactory, especially in mycosis fungoides (MF). Therefore, additional drugs to enhance the antitumor effects of mogamulizumab is needed to further optimize its use for the treatment of MF. In this report,two cases of mogamulizumab‐resistant MF successfully treated with additional administration of etoposide are presented. Moreover, the possible mechanisms of mogamulizumab‐etoposide combined therapy for the treatment of MF were investigated based on the modulation of chemokine profiles in vivo using an EL‐4 mouse T cell lymphoma model.Intraperitoneal administration of etoposide significantly increased the mRNA expressions of CCL17, CXCL5, and CXCL10, suggesting that CCR4+ CTCL cells gather around the TAMs. Furthermore, the immunomodulatory effects of etoposide on the mRNA expressions of these chemokines were validated using monocyte‐derived M2 macrophages in vitro. Since mogamulizumab showscytotoxicity against CCR4+ lymphoma cells by ADCC that depends on the contact between the lymphoma cellsand the effector cells, these chemokines could enhance the therapeutic effect of mogamulizumab.Keywords
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