期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 67, 期 3, 页码 423-434出版社
SPRINGER
DOI: 10.1007/s00262-017-2090-z
关键词
T regulatory cells; Myeloid-derived suppressor cells; Cutaneous T-cell lymphoma; Sezary syndrome; Mycosis fungoides
资金
- Research Center Grants for Specialized Programs of Research of Excellence of National Institute of Health, Clinical and Translational Science [P50CA121973]
- M01 Award of National Center for Research Resources
Tumor progression is associated with progressive immunosuppression mediated in part by T regulatory cell(s) (Treg) and/or myeloid-derived suppressor cell(s) (MDSC). Development of strategies to reduce populations of immune cells with suppressive function in cancer patients may enable the induction or recovery of immunity against tumor cells, which may limit or reverse disease progression. With a goal of developing Treg and MDSC neutralizing strategies to treat mycosis fungoides (MF) and Sezary syndrome (SzS), we determined the association between disease stage and suppressor cell populations in patients with MF/SzS, including those responding to therapy. We found elevations in Treg populations, across Treg subtypes, in patients with SzS, and these Treg markedly suppressed proliferation of autologous -CD4(+) CD25(-) responder T cells. Interestingly, while MDSC numbers were not increased in MF/SzS patients, MDSC from patients with stage IB and above produced significantly more reactive oxygen species than those from stage IA MF patients and control cohorts. Therapy with the CD25-targeting agent denileukin diftitox or IFN-alpha 2b was associated with a reduction in Treg numbers or MDSC function, respectively. These studies identify potential mechanisms of action for these therapies and support the development of coordinated strategies targeting both Treg and MDSC activities in patients with MF/SzS.
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