scholarly journals Programmed cell death 1‐expressing CD56‐negative natural killer (NK) cell expansion is a hallmark of chronic NK cell activation during dasatinib treatment

2020 ◽  
Author(s):  
Ken‐ichi Ishiyama ◽  
Toshio Kitawaki ◽  
Yasuyuki Otsuka ◽  
Akifumi Takaori‐Kondo ◽  
Norimitsu Kadowaki
2012 ◽  
Vol 209 (6) ◽  
pp. 1201-1217 ◽  
Author(s):  
Tadashi Yokosuka ◽  
Masako Takamatsu ◽  
Wakana Kobayashi-Imanishi ◽  
Akiko Hashimoto-Tane ◽  
Miyuki Azuma ◽  
...  

Programmed cell death 1 (PD-1) is a negative costimulatory receptor critical for the suppression of T cell activation in vitro and in vivo. Single cell imaging elucidated a molecular mechanism of PD-1–mediated suppression. PD-1 becomes clustered with T cell receptors (TCRs) upon binding to its ligand PD-L1 and is transiently associated with the phosphatase SHP2 (Src homology 2 domain–containing tyrosine phosphatase 2). These negative costimulatory microclusters induce the dephosphorylation of the proximal TCR signaling molecules. This results in the suppression of T cell activation and blockade of the TCR-induced stop signal. In addition to PD-1 clustering, PD-1–TCR colocalization within microclusters is required for efficient PD-1–mediated suppression. This inhibitory mechanism also functions in PD-1hi T cells generated in vivo and can be overridden by a neutralizing anti–PD-L1 antibody. Therefore, PD-1 microcluster formation is important for regulation of T cell activation.


2019 ◽  
Vol 143 (1) ◽  
pp. 78-88 ◽  
Author(s):  
Hamidah Muhamad ◽  
Narittee Suksawai ◽  
Thamatorn Assanasen ◽  
Chantana Polprasert ◽  
Udomsak Bunworasate ◽  
...  

The programmed cell death 1/programmed cell death ligands (PD-1/PD-Ls) axis is a potential immune escape mechanism of cancers. However, data on the PD-1/PD-Ls pathway in EBV-associated extranodal natural killer/T cell lymphoma (ENKTL) and its clinical implication are limited. Herein, we characterized PD-1/PD-L expression and its prognosis relevance in 49 ENKTL patients in Thailand. PD-L1 was expressed frequently on both lymphoma cells (61.2%) and stroma (77.5%), whereas PD-L2 expression was more common on lymphoma (63.2%) than stromal cells. PD-1 was positive in 20.5% of stroma, but undetectable on lymphoma cells. There was no association between baseline clinical characteristics and the expression PD-1/PD-Ls. The survival of patients with PD-Ls on tumor cells was poor. For PD-L1-positive versus negative cases, the 2-year event-free survival (EFS) was 42.2 versus 71.8% (p = 0.03) and 2-year overall survival (OS) was 45.4 versus 78.9% (p = 0.02), respectively. Comparing between patients with PD-L2-positive and PD-L2-negative lymphoma, the 2-year EFS was 37.1 versus 82.4% (p = 0.02) and 2-year OS was 45.2 versus 82.4% (p = 0.03), respectively. Neither PD-1 nor PD-Ls expression in the stroma predicted outcomes. In conclusion, PD-Ls were frequently expressed on ENKTL cells and associated with inferior outcomes. Therefore, PD-Ls are potential prognostic biomarkers and the roles of immune checkpoint blockade therapy in ENKTL deserve further investigation.


2010 ◽  
Vol 185 (5) ◽  
pp. 2754-2762 ◽  
Author(s):  
Oliver T. Burton ◽  
Paola Zaccone ◽  
Jenny M. Phillips ◽  
Hugo De La Peña ◽  
Zoltán Fehérvári ◽  
...  

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e93280 ◽  
Author(s):  
Clément Cochain ◽  
Sweena M. Chaudhari ◽  
Miriam Koch ◽  
Heinz Wiendl ◽  
Hans-Henning Eckstein ◽  
...  

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