PD-1 suppresses the maintenance of cell couples between cytotoxic T cells and target tumor cells within the tumor.
PD-1 suppresses the maintenance of cell couples between cytotoxic T cells and target tumor cells within the tumor.
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DOI：
10.1126/scisignal.aau4518
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发表时间：
2020-09-15
影响因子：
7.3
通讯作者：
Wülfing C
中科院分区：
文献类型：
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作者：
Ambler R;Edmunds GL;Tan SL;Cirillo S;Pernes JI;Ruan X;Huete-Carrasco J;Wong CCW;Lu J;Ward J;Toti G;Hedges AJ;Dovedi SJ;Murphy RF;Morgan DJ;Wülfing C
The killing of tumor cells by CD8+ T cells is suppressed by the tumor microenvironment, and increased expression of inhibitory receptors, including programmed cell death protein-1 (PD-1), is associated with tumor-mediated suppression of T cells. To discover cellular defects triggered by tumor exposure and associated PD-1 signaling, we established an ex vivo imaging approach to investigate the response of antigen-specific, activated effector CD8+ Tumor infiltrating淋巴细胞（TIL）与目标肿瘤细胞相互作用。类似的表型，支持直接的T细胞肿瘤接触会减少PD-1在肿瘤中的接合，但急性的离体封锁，部分恢复了细胞夫妇的维持和杀伤。
The killing of tumor cells by CD8+ T cells is suppressed by the tumor microenvironment, and increased expression of inhibitory receptors, including programed cell death protein-1 (PD-1), is associated with tumor-mediated suppression of T cells. To discover cellular defects triggered by tumor exposure and associated PD-1 signaling, we established an ex vivo imaging approach to investigate the response of antigen-specific, activated effector CD8+ tumor infiltrating lymphocytes (TILs) after interaction with target tumor cells. Although TIL–tumor cell couples readily formed, couple stability deteriorated within minutes. This was associated with impaired F-actin clearing from the center of the cellular interface, reduced Ca2+ signaling, increased TIL locomotion, and impaired tumor cell killing. The interaction of CD8+ T lymphocytes with tumor cell spheroids in vitro induced a similar phenotype, supporting a critical role of direct T cell–tumor cell contact. Diminished engagement of PD-1 within the tumor, but not acute ex vivo blockade, partially restored cell couple maintenance and killing. PD-1 thus contributes to the suppression of TIL function by inducing a state of impaired subcellular organization.
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影响因子：
21.3
作者：
Gohla, A;Birkenfeld, J;Bokoch, GM
通讯作者：
Bokoch, GM
DOI：
10.1084/jem.20061890
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Boissonnas A;Fetler L;Zeelenberg IS;Hugues S;Amigorena S
通讯作者：
Amigorena S
影响因子：
4.4
作者：
Chemnitz, JM;Parry, RV;Riley, JL
通讯作者：
Riley, JL
影响因子：
8.7
作者：
Babich A;Burkhardt JK
通讯作者：
Burkhardt JK
影响因子：
8.7
作者：
通讯作者：
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