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CD15+/CD16low human granulocytes from terminal cancer patients: granulocytic myeloid-derived suppressor cells that have suppressive function

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Tumor Biology

Abstract

Myeloid-derived suppressor cells (MDSCs) are a subpopulation of myeloid cells with immunosuppressive function whose numbers are increased in conditions such as chronic infection, trauma, and cancer. Unlike murine MDSCs defined as CD11b+/Gr-1+, there are no specific markers for human MDSCs. The goal of this study was to delineate a specific human MDSCs subpopulation in granulocytes from terminal cancer patients and investigate its clinical implications. Here, we show that the CD15+/CD16low subset was increased in terminal cancer patients compared with healthy donors (P = 0.009). Phorbol 12-myristate 13-acetate-activated granulocytes (CD16low/CD66b++/CD15+) that have a phenotype similar to MDSCs from cancer patients, effectively suppressed both proliferation and cytotoxicity of normal T cells. Among cancer patients, T-cell proliferation was highly suppressed by granulocytes isolated from terminal cancer patients with a high proportion of CD15+/CD16low cells. Patients with low peripheral blood levels of CD15+/CD16low cells had significantly longer survival than those with high levels (P = 0.0011). Patients with higher levels of CD15+/CD16low also tended to have poor performance status (P = 0.05). These data suggest that CD15+/CD16low granulocytes found in terminal cancer patients may play a role in the progression of cancer by inhibiting tumor immunity.

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Acknowledgements

We thank all the staff from the Department of Internal Medicine, Seoul National University Hospital, for recruiting the patients for this study. This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A062260).

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Authors and Affiliations

  1. Cancer Research Institute, Seoul National University College of Medicine and Hospital, Seoul, South Korea

    Jahyang Choi, Beomseok Suh, Yong-Oon Ahn, Tae Min Kim, Jeong-Ok Lee, Se-Hoon Lee & Dae Seog Heo

  2. Innovative Research Institute for Cell Therapy, Seoul National University College of Medicine and Hospital, Seoul, South Korea

    Jahyang Choi, Yong-Oon Ahn, Tae Min Kim, Se-Hoon Lee & Dae Seog Heo

  3. Department of Internal Medicine, Seoul National University College of Medicine and Hospital, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, South Korea

    Tae Min Kim, Jeong-Ok Lee, Se-Hoon Lee & Dae Seog Heo

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  1. Jahyang Choi
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Correspondence to Dae Seog Heo.

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Choi, J., Suh, B., Ahn, YO. et al. CD15+/CD16low human granulocytes from terminal cancer patients: granulocytic myeloid-derived suppressor cells that have suppressive function. Tumor Biol. 33, 121–129 (2012). https://doi.org/10.1007/s13277-011-0254-6

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  • DOI: https://doi.org/10.1007/s13277-011-0254-6

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