title: CD15+/CD16low human granulocytes from terminal cancer patients: granulocytic myeloid-derived suppressor cells that have suppressive function.
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(+)/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.
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine and Hospital, Seoul, South Korea.
authors.forename: Jahyang
authors.initials: J
authors.lastname: Choi
authors.forename: Beomseok
authors.initials: B
authors.lastname: Suh
authors.forename: Yong-Oon
authors.initials: YO
authors.lastname: Ahn
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.forename: Jeong-Ok
authors.initials: JO
authors.lastname: Lee
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007958:Leukocyte Count; D016256:Lewis X Antigen / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
chemical_list: D016256:Lewis X Antigen; D017452:Receptors, IgG
references.citation: Cancer Immunol Immunother. 2008 Oct;57(10):1493-504
references.pmid: 18322683
references.citation: J Immunol. 2008 Oct 15;181(8):5791-802
references.pmid: 18832739
references.citation: Cancer Res. 2001 Jun 15;61(12):4756-60
references.pmid: 11406548
references.citation: J Immunol. 2000 Dec 15;165(12):6723-30
references.pmid: 11120790
references.citation: Eur J Immunol. 2009 Oct;39(10):2865-76
references.pmid: 19637228
references.citation: Cancer Immunol Immunother. 2009 Jan;58(1):49-59
references.pmid: 18446337
references.citation: Shock. 2000 May;13(5):361-6
references.pmid: 10807010
references.citation: Curr Opin Immunol. 2010 Apr;22(2):238-44
references.pmid: 20171075
references.citation: Cancer Res. 2009 Feb 15;69(4):1553-60
references.pmid: 19201693
references.citation: J Leukoc Biol. 2009 Jun;85(6):996-1004
references.pmid: 19261929
references.citation: Gastroenterology. 2008 Jul;135(1):234-43
references.pmid: 18485901
references.citation: Blood. 1995 Jan 15;85(2):532-40
references.pmid: 7812008
references.citation: Blood. 2005 Mar 15;105(6):2549-56
references.pmid: 15546957
references.citation: Nat Med. 2007 Jul;13(7):828-35
references.pmid: 17603493
references.citation: Nat Rev Immunol. 2005 Aug;5(8):641-54
references.pmid: 16056256
references.citation: Cancer Cell. 2008 Nov 4;14(5):408-19
references.pmid: 18977329
references.citation: J Immunol. 1994 Aug 1;153(3):1254-63
references.pmid: 8027553
references.citation: Crit Care Med. 2004 Jul;32(7):1604-6
references.pmid: 15241110
references.citation: Blood. 2008 Apr 15;111(8):4233-44
references.pmid: 18272812
references.citation: Cancer Immunol Immunother. 2011 Oct;60(10):1419-30
references.pmid: 21644036
references.citation: J Immunol. 2002 Jan 15;168(2):689-95
references.pmid: 11777962
references.citation: Immunol Res. 2011 Aug;50(2-3):153-8
references.pmid: 21717065
references.citation: J Clin Oncol. 2007 Jun 20;25(18):2546-53
references.pmid: 17577033
references.citation: Clin Cancer Res. 2007 Jan 15;13(2 Pt 2):721s-726s
references.pmid: 17255300
references.citation: J Immunol. 2009 Apr 15;182(8):4499-506
references.pmid: 19342621
references.citation: Cancer Res. 2005 Apr 15;65(8):3044-8
references.pmid: 15833831
references.citation: J Immunol. 2004 Jan 15;172(2):989-99
references.pmid: 14707072
references.citation: J Immunol. 2001 Jan 1;166(1):678-89
references.pmid: 11123353