CEACAM1 dampens antitumor immunity by down-regulating NKG2D ligand expression on tumor cells

Zhangguo Chen; Lanfen Chen; Kristi Baker; Torsten Olszak; Sebastian Zeissig; Yu Hwa Huang; Timothy T. Kuo; Ofer Mandelboim; Nicole Beauchemin; Lewis L. Lanier; Richard S. Blumberg

doi:10.1084/jem.20102575

CEACAM1 dampens antitumor immunity by down-regulating NKG2D ligand expression on tumor cells

Zhangguo Chen, Lanfen Chen, Kristi Baker, Torsten Olszak, Sebastian Zeissig, Yu Hwa Huang, Timothy T. Kuo, Ofer Mandelboim, Nicole Beauchemin, Lewis L. Lanier, Richard S. Blumberg

Department of Immunology and Cancer Research

The Hebrew University of Jerusalem

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	2633-2640
Number of pages	8
Journal	Journal of Experimental Medicine
Volume	208
Issue number	13
DOIs	https://doi.org/10.1084/jem.20102575
State	Published - 19 Dec 2011

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1084/jem.20102575

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title = "CEACAM1 dampens antitumor immunity by down-regulating NKG2D ligand expression on tumor cells",

abstract = "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.",

author = "Zhangguo Chen and Lanfen Chen and Kristi Baker and Torsten Olszak and Sebastian Zeissig and Huang, {Yu Hwa} and Kuo, {Timothy T.} and Ofer Mandelboim and Nicole Beauchemin and Lanier, {Lewis L.} and Blumberg, {Richard S.}",

year = "2011",

month = dec,

day = "19",

doi = "10.1084/jem.20102575",

language = "الإنجليزيّة",

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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.

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U2 - 10.1084/jem.20102575

DO - 10.1084/jem.20102575

M3 - مقالة

C2 - 22143889

SN - 0022-1007

VL - 208

SP - 2633

EP - 2640

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 13

ER -

CEACAM1 dampens antitumor immunity by down-regulating NKG2D ligand expression on tumor cells

Abstract

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