scholarly journals Apoptosis-Independent Reduction of Programmed Death Ligand-1 Levels by Boningmycin Through AMPK-Mediated Endoplasmic Reticulum-Associated Protein Degradation in Human Tumor Cells

2021 ◽  
Author(s):  
Juan Zhang ◽  
Jin-Cai Wang ◽  
Yue Shang ◽  
Yang Chen ◽  
Shu-Zhen Chen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Tumor Cells ◽  
Specific Inhibitor ◽  
Degradation Pathway ◽  
Programmed Death Ligand 1 ◽  
Protein Levels ◽  
Compound C ◽  
Endoplasmic Reticulum Associated Degradation ◽  
Programmed Death ◽  
L1 Protein

Abstract Boningmycin (BON), a new member of the bleomycin family, exhibits highly potent activity against tumor cells in vitro and in vivo. It remains unclear if BON can affect the protein levels of programmed death ligand-1 (PD-L1) in a manner similar to that of other antitumor agents. Potent inhibition of cell survival by BON was observed in non-small-cell lung cancer NCI-H460 cells and sarcoma HT1080 cells. Apoptosis-independent reduction of PD-L1 was observed after exposure to BON. Furthermore, BON-treatment increased AMP-activated protein kinase phosphorylation, however, this increase was suppressed by treatment with specific inhibitor (compound C) or RNAi-mediated knockdown of AMPKα. BON-induced PD-L1 reduction is mediated by the endoplasmic reticulum-associated degradation pathway. Its mode of action is similar to that of metformin on the PD-L1 protein. In conclusion, it is firstly reported that BON can decrease PD-L1 protein levels through the AMPK activated endoplasmic reticulum- associated degradation pathway.

scholarly journals Programmed Death Ligand-1 (PD-L1) Expression in Either Tumor Cells or Tumor-Infiltrating Immune Cells Correlates With Solid and High-Grade Lung Adenocarcinomas

2017 ◽  
Vol 141 (11) ◽  
pp. 1529-1532 ◽  
Author(s):  
Brandon R. Driver ◽  
Ross A. Miller ◽  
Tara Miller ◽  
Michael Deavers ◽  
Blythe Gorman ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
Histologic Grade ◽  
Fisher Exact Test ◽  
Clinicopathologic Features ◽  
Cell Lung Carcinoma ◽  
Programmed Death Ligand 1 ◽  
Exact Test ◽  
Programmed Death ◽  
High Histologic Grade

Context.— Programmed death ligand-1 (PD-L1) expression in non–small cell lung carcinoma (NSCLC) is heterogeneous and known to be underestimated on small biopsies. Correlation of PD-L1 expression with clinicopathologic features may provide additional useful information. To our knowledge, the clinicopathologic features of NSCLC have not been reported for subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells. Objective.— To investigate the clinicopathologic characteristics of NSCLC subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells. Design.— PD-L1 immunohistochemistry with the SP142 clone was performed on whole-tissue sections and given semiquantitative scores (0/1/2/3) according to percent of PD-L1+ tumor cells (TCs) and percent tumor area with PD-L1+ tumor-infiltrating immune cells (ICs). Results.— Adenocarcinoma cases that were scored either TC 1/2/3 or IC 1/2/3 included most (22 of 34; 65%) high–histologic grade cases and most (25 of 36; 69%) solid subtype cases. Compared with the adenocarcinoma TC 0 and IC 0 subset, the TC 1/2/3 or IC 1/2/3 subset correlated with higher histologic grade (P = .005, χ2 test for trend) and solid subtype (P < .001, Fisher exact test). Compared with the adenocarcinoma TC 0/1 or IC 0/1 subset, the TC 2/3 or IC 2/3 subset correlated with higher histologic grade (P = .002, χ2 test for trend), solid subtype (P < .001, Fisher exact test), and higher smoking pack-years (P = .01, Mann-Whitney test). Conclusions.— Lung adenocarcinoma subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells correlated with high histologic grade, solid subtype, and high smoking pack-years.

scholarly journals P2.04-01 Associations Histological Subtype of Lung Adenocarcinoma and Programmed Death Ligand 1 (PD-L1) Expression in Tumor Cells.

2018 ◽  
Vol 13 (10) ◽  
pp. S730
Author(s):  
G. Cruz-Rico ◽  
X. Popa Navarro ◽  
A. Avilés-Salas ◽  
K.Y. Flores-Vélez ◽  
A. Cardona ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Histological Subtype ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

scholarly journals Evaluation of hepatocellular carcinoma circulating tumor cells expressing programmed death-ligand 1

HPB ◽  
2018 ◽  
Vol 20 ◽  
pp. S2-S3 ◽  
Author(s):  
P. Winograd ◽  
S. Hou ◽  
C.M. Court ◽  
S. Sadeghi ◽  
R.S. Finn ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

scholarly journals Salmonella Breaks Tumor Immune Tolerance by Downregulating Tumor Programmed Death-Ligand 1 Expression

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 57
Author(s):  
Man-Chin Chen ◽  
Christian Ronquillo Pangilinan ◽  
Che-Hsin Lee
Keyword(s):  
T Cell ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Immune Checkpoint ◽  
Immune Escape ◽  
Cell Infiltration ◽  
Tumor Immune Escape ◽  
Programmed Death Ligand 1 ◽  
T Cell Infiltration ◽  
Programmed Death

Immunotherapy is becoming a popular treatment modality in combat against cancer, one of the world’s leading health problems. While tumor cells influence host immunity via expressing immune inhibitory signaling proteins, some bacteria possess immunomodulatory activities that counter the symptoms of tumors. The accumulation of Salmonella in tumor sites influences tumor protein expression, resulting in T cell infiltration. However, the molecular mechanism by which Salmonella activates T cells remains elusive. Many tumors have been reported to have high expressions of programmed death-ligand 1 (PD-L1), which is an important immune checkpoint molecule involved in tumor immune escape. In this study, Salmonella reduced the expression of PD-L1 in tumor cells. The expression levels of phospho-protein kinase B (P-AKT), phospho-mammalian targets of rapamycin (P-mTOR), and the phospho-p70 ribosomal s6 kinase (P-p70s6K) pathway were revealed to be involved in the Salmonella-mediated downregulation of PD-L1. In a tumor-T cell coculture system, Salmonella increased T cell number and reduced T cell apoptosis. Systemic administration of Salmonella reduced the expressions of PD-L-1 in tumor-bearing mice. In addition, tumor growth was significantly inhibited along with an enhanced T cell infiltration following Salmonella treatment. These findings suggest that Salmonella acts upon the immune checkpoint, primarily PD-L1, to incapacitate protumor effects and thereby inhibit tumor growth.

Programmed Death Ligand 1 Expression Among 700 Consecutive Endometrial Cancers: Strong Association With Mismatch Repair Protein Deficiency

2018 ◽  
Vol 28 (1) ◽  
pp. 59-68 ◽  
Author(s):  
Zaibo Li ◽  
Amy S. Joehlin-Price ◽  
Jennifer Rhoades ◽  
Martins Ayoola-Adeola ◽  
Karin Miller ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Tumor Cells ◽  
Strong Association ◽  
Significant Proportion ◽  
Programmed Death Ligand 1 ◽  
Tumor Immune Evasion ◽  
Kaplan Meier ◽  
Programmed Death ◽  
Adjusted Logistic Regression ◽  
Histologic Types

ObjectiveThis study aims to determine the prevalence of programmed death ligand 1 (PD-L1) expression in endometrial carcinoma (EC) and determine clinical and pathological associations.MethodsImmunohistochemistry for PD-L1 was performed on sections of a triple-core tissue microarray of 700 ECs. Positive PD-L1 expression, defined as 1% of cells staining positive, was evaluated in tumor and stromal compartments. Using age-adjusted logistic regression, we estimated odds ratios and 95% confidence intervals for associations between PD-L1 expression (overall and by staining compartment) with clinical and tumor characteristics. Kaplan-Meier plots and log-rank tests were used to evaluate associations between PD-L1 expression and EC-specific survival.ResultsPD-L1 expression was observed in 100 cases (14.3%), including 27 (3.9%) with expression in tumor cells only, 35 (5.0%) with expression in both tumor cells and stroma, and 38 (5.4%) with expression in stroma only. Expression was observed in ECs of different histologic types. Tumors characterized by loss of mismatch repair proteins were significantly associated with tumoral PD-L1 expression (P< 0.0001), but not with stromal PD-L1 expression. Both tumoral and stromal PD-L1 expressions were associated with high-grade endometrioid histology, nonendometrioid histology, and lymphovascular space invasion. We observed no significant associations between PD-L1 expression and EC-specific survival.ConclusionsPD-L1 is expressed in a significant proportion of EC and is associated with mismatch repair deficiency, potentially representing a mechanism of tumor immune evasion and a therapeutic target in EC.

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