Peritoneal natural killer cells from epithelial ovarian cancer patients show an altered phenotype and bind to the tumour marker MUC16 (CA125).
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.
Belisle
Jennifer A
JA
Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, WI 53792, USA.
Gubbels
Jennifer A A
JA
Raphael
Cara A
CA
Migneault
Martine
M
Rancourt
Claudine
C
Connor
Joseph P
JP
Patankar
Manish S
MS
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
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