CD15⁺/CD16^low human granulocytes from terminal cancer patients: granulocytic myeloid-derived suppressor cells that have suppressive function

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⁺/CD16^low subset was increased in terminal cancer patients compared with healthy donors (P = 0.009). Phorbol 12-myristate 13-acetate-activated granulocytes (CD16^low/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⁺/CD16^low cells. Patients with low peripheral blood levels of CD15⁺/CD16^low cells had significantly longer survival than those with high levels (P = 0.0011). Patients with higher levels of CD15⁺/CD16^low also tended to have poor performance status (P = 0.05). These data suggest that CD15⁺/CD16^low granulocytes found in terminal cancer patients may play a role in the progression of cancer by inhibiting tumor immunity.