Galectin-9 as a predictive marker for the onset of immunerelated adverse effects associated with anti-CCR4 MoAb therapy in patients with adult T cell leukemia

Tareg Omer Mohammed, Haorile Chagan-Yasutan, Yugo Ashino, Wakana Nakayama, Yayoi Takahashi, Taizo Shimomura, Tetsuhiro Fujimoto, Yuko Watanabe, Toshiro Niki, Hitoshi Suzushima, Toshio Hattori

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Adult T-cell leukemia/lymphoma (ATL/ATLL) is one of the most malignant lymphomas with poor prognosis. ATL/ATLL cells express CC chemokine receptor 4, and mogamulizumab (anti-CCR4 monoclonal antibody) exhibits strong cytotoxicity for ATL/ATLL cells. We analyzed plasma samples of 6 patients with ATL/ATLL treated with chemotherapy followed by mogamulizumab therapy (mogatherapy) for changes in the levels of biomarkers in relation to immune-related adverse effects. As treatment is often associated with skin eruptions, we investigated the profiles of inflammatory cytokines, including galectin-9 (Gal-9), which becomes increased in various infectious diseases and allergic patients. Gal-9, soluble interleukin (IL)-2 receptor, tumor necrosis factor-α, and IL-10 levels were increased before chemotherapy, and Gal-9 levels were associated with the sIL-2 receptor, which reflects tumor burden. Inflammatory levels decreased after chemotherapy. After mogatherapy, 5 of 6 patients attained complete remission (CR), whereas 1 patient showed no response (NR) and died. Among 5 patients with CR, the biomarkers remained low during mogatherapy, except for a 3-5-fold increment in Gal-9 (associated with skin eruptions). A skin biopsy showed infiltration by inflammatory cells and Gal-9 synthesis in areas with CD8 cell infiltration. In the patient with NR, increased levels of Gal-9 and the aforementioned biomarkers were noted 3 days after mogatherapy, followed by opportunistic infections resembling immune reconstitution inflammatory syndrome. Therefore, an increased Gal-9 plasma level in ATL/ATLL indicates tumor burden and reflects immune activation by mogatherapy. These findings may indicate that an increase in the Gal-9 level, a novel immune checkpoint molecule, can reflect immune-related adverse effects of various biotherapies.

Original languageEnglish
Pages (from-to)201-208
Number of pages8
JournalTohoku Journal of Experimental Medicine
Volume241
Issue number3
DOIs
Publication statusPublished - 2017 Mar

Keywords

  • Adult T-cell leukemia/lymphoma
  • Galectin-9
  • Immune reconstitution inflammatory syndrome
  • Mogamulizumab
  • Skin eruption

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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