TY - JOUR
T1 - CEACAM1 dampens antitumor immunity by down-regulating NKG2D ligand expression on tumor cells
AU - Chen, Zhangguo
AU - Chen, Lanfen
AU - Baker, Kristi
AU - Olszak, Torsten
AU - Zeissig, Sebastian
AU - Huang, Yu Hwa
AU - Kuo, Timothy T.
AU - Mandelboim, Ofer
AU - Beauchemin, Nicole
AU - Lanier, Lewis L.
AU - Blumberg, Richard S.
PY - 2011/12/19
Y1 - 2011/12/19
N2 - Although carcinoembryonic antigen (CEA)-related cell adhesion molecule 1 (CEACAM1) has been viewed as a tumor suppressor, increasing clinical evidence shows that high levels of CEACAM1 expression on tumors correlates with poor prognosis and high risk of metastasis. Here, we examined the consequences of CEACAM1 expression on tumor cells. We show that tumor cell-associated CEACAM1 causes intracellular retention of various NKG2D ligands in mouse and human tumor cells. CEACAM1-silenced tumor cells expressed more cell surface NKG2D ligands and exhibited greater sensitivity to natural killer cell-mediated cytolysis in vitro and rejection in vivo. Our studies reveal a novel mechanism through which CEACAM1-bearing tumor cells may escape immune-surveillance.
AB - Although carcinoembryonic antigen (CEA)-related cell adhesion molecule 1 (CEACAM1) has been viewed as a tumor suppressor, increasing clinical evidence shows that high levels of CEACAM1 expression on tumors correlates with poor prognosis and high risk of metastasis. Here, we examined the consequences of CEACAM1 expression on tumor cells. We show that tumor cell-associated CEACAM1 causes intracellular retention of various NKG2D ligands in mouse and human tumor cells. CEACAM1-silenced tumor cells expressed more cell surface NKG2D ligands and exhibited greater sensitivity to natural killer cell-mediated cytolysis in vitro and rejection in vivo. Our studies reveal a novel mechanism through which CEACAM1-bearing tumor cells may escape immune-surveillance.
UR - http://www.scopus.com/inward/record.url?scp=84862908667&partnerID=8YFLogxK
U2 - 10.1084/jem.20102575
DO - 10.1084/jem.20102575
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C2 - 22143889
AN - SCOPUS:84862908667
SN - 0022-1007
VL - 208
SP - 2633
EP - 2640
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 13
ER -