title: Peritoneal natural killer cells from epithelial ovarian cancer patients show an altered phenotype and bind to the tumour marker MUC16 (CA125).
abstract: The ovarian tumour marker MUC16 (CA125) inhibits the cytotoxic responses of human natural killer (NK) cells and down-regulates CD16. Here we show that approximately 10% of the peripheral blood NK cells (PBNK) from the epithelial ovarian cancer (EOC) patients are CD16(-) CD56(br) whereas 40% of the peritoneal fluid NK (PFNK) carry this phenotype, which is usually associated with NK cells from the lymph nodes or human decidua. PBNK from healthy donors exposed to PF show a significant increase in the CD16(-) CD56(br) population. This shift in phenotype is not caused by increased apoptosis of the CD16(+) CD56(dim) cells or selective proliferation of the CD16(-) CD56(br) NK cells. Thus, the terminal differentiation of the CD16(-) CD56(br) NK cells to CD16(+) CD56(dim) subset that occurs during normal NK cell development may actually be a reversible step. A majority of the NK cell receptors (NKp46, NKp44, NKG2D, CD244, CD226, CD158a, CD158b, and CD158e) studied were down-regulated in the PFNK. MUC16 binds selectively to 30-40% of CD16(+) CD56(dim) NK cells in EOC patients indicating that phenotypic alterations in these cells are mediated by tumour-derived soluble factors. Similar to EOC, MUC16 in early pregnancy also binds to NK cells suggesting shared mechanisms of NK cell suppression in feto-maternal tolerance and immune evasion by ovarian cancers.
authors.affiliation: Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, WI 53792, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Belisle
authors.forename: Jennifer A A
authors.initials: JA
authors.lastname: Gubbels
authors.forename: Cara A
authors.initials: CA
authors.lastname: Raphael
authors.forename: Martine
authors.initials: M
authors.lastname: Migneault
authors.forename: Claudine
authors.initials: C
authors.lastname: Rancourt
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Connor
authors.forename: Manish S
authors.initials: MS
authors.lastname: Patankar
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D001202:Ascitic Fluid / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018394:CA-125 Antigen / Q000378:metabolism*; D019002:CD56 Antigen / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000276:immunology*; D011247:Pregnancy / Q000276:immunology; D017452:Receptors, IgG / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D019002:CD56 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; C451759:MUC16 protein, human; D008565:Membrane Proteins; D017452:Receptors, IgG