Primary human tumor cells expressing CD155 impair tumor targeting by down-regulating DNAM-1 on NK cells.
The activating NK cell receptor DNAX accessory molecule-1 (DNAM-1) contributes to tumor immune surveillance and plays a crucial role in NK cell-mediated recognition of several types of human tumors, including ovarian carcinoma. Here, we have analyzed the receptor repertoire and functional integrity of NK cells in peritoneal effusions from patients with ovarian carcinoma. Relative to autologous peripheral blood NK cells, tumor-associated NK cells expressed reduced levels of the DNAM-1, 2B4, and CD16 receptors and were hyporesponsive to HLA class I-deficient K562 cells and to coactivation via DNAM-1 and 2B4. Moreover, tumor-associated NK cells were also refractory to CD16 receptor stimulation, resulting in diminished Ab-dependent cellular cytotoxicity against autologous tumor cells. Coincubation of NK cells with ovarian carcinoma cells expressing the DNAM-1 ligand CD155 led to reduction of DNAM-1 expression. Therefore, NK cell-mediated rejection of ovarian carcinoma may be limited by perturbed DNAM-1 expression on tumor-associated NK cells induced by chronic ligand exposure. Thus, these data support the notion that tumor-induced alterations of activating NK cell receptor expression may hamper immune surveillance and promote tumor progression.
Carlsten
Mattias
M
Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Center for Infectious Medicine, Stockholm, Sweden. mattias.carlsten@ki.se
Norell
Håkan
H
Bryceson
Yenan T
YT
Poschke
Isabel
I
Schedvins
Kjell
K
Ljunggren
Hans-Gustaf
HG
Kiessling
Rolf
R
Malmberg
Karl-Johan
KJ
D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D001202:Ascitic Fluid / Q000276:immunology / Q000378:metabolism; D002277:Carcinoma / Q000276:immunology* / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D011991:Receptors, Virus / Q000276:immunology / Q000378:metabolism*; D000071176:Signaling Lymphocytic Activation Molecule Family; D000098862:T Lineage-Specific Activation Antigen 1
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; C084093:CD244 protein, human; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D011991:Receptors, Virus; D000071176:Signaling Lymphocytic Activation Molecule Family; C066100:poliovirus receptor