scholarly journals Programmed Death Ligand 1: A Poor Prognostic Marker in Endometrial Carcinoma

Diagnostics ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 394
Author(s):  
Mianxin Chew ◽  
Yin Ping Wong ◽  
Norain Karim ◽  
Muaatamarulain Mustangin ◽  
Nurwardah Alfian ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
Immune Cells ◽  
Immune Cell ◽  
Tumour Cells ◽  
Health Concern ◽  
Major Health ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Incidence And Mortality ◽  
Gynaecologic Malignancy

Endometrial carcinoma is the only gynaecologic malignancy with a raising incidence and mortality, posing a major health concern worldwide. The upregulation of programmed death ligand 1 (PD-L1) on tumour cells causes T-cell suppression, which impedes antitumour immunity, promotes immune cell evasion and enhances tumour survival. The aim of this study was to evaluate PD-L1 expression in endometrial carcinoma and to correlate it with survival rate. A total of 59 cases of endometrial carcinoma were evaluated. Thirty-two cases of non-neoplastic endometrial tissue were included as control. PD-L1 immunohistochemistry was performed on all cases. PD-L1 expression was evaluated on tumour cells and immune cells. PD-L1 was positive in 62.7% (37/59) and 28.8% (17/59) of immune cells and tumour cells, respectively. PD-L1 expression in immune cells was significantly higher in endometrial carcinoma than in non-neoplastic endometrium (p < 0.001). Among the patients with endometrial carcinoma, PD-L1 expression in tumour cells was significantly higher in patients who died (10/15, 66.7%) compared to those who survived (7/44, 15.9%) (p < 0.001). It is noteworthy to point out that the expression of PD-L1 in tumour cells was significantly associated with a poor survival. This suggests that immunomodulation using PD-L1 inhibitors may be useful in advanced endometrial carcinoma.

scholarly journals Analytical Validation and Clinical Utility of an Immunohistochemical Programmed Death Ligand-1 Diagnostic Assay and Combined Tumor and Immune Cell Scoring Algorithm for Durvalumab in Urothelial Carcinoma

2018 ◽  
Vol 143 (6) ◽  
pp. 722-731 ◽  
Author(s):  
Magdalena Zajac ◽  
Anne-Marie Boothman ◽  
Yong Ben ◽  
Ashok Gupta ◽  
Xiaoping Jin ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Tumor Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Objective Response ◽  
Clinical Activity ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Sensitivity Specificity ◽  
Tumor Area

Context.— Clinical responses to anti–programmed death receptor-1 and anti–programmed death ligand-1 (PD-L1) agents are generally improved in patients with high PD-L1 expression compared with those with low/negative expression across several tumor types, including urothelial carcinoma. Objective.— To validate a PD-L1 immunohistochemical diagnostic test in urothelial carcinoma patients treated with the anti–PD-L1 monoclonal antibody durvalumab. Design.— The Ventana PD-L1 (SP263) assay was validated for intended use in urothelial carcinoma formalin-fixed, paraffin-embedded samples in studies addressing sensitivity, specificity, robustness, and precision, and implemented in study CD-ON-MEDI4736-1108 (NCT01693562). Efficacy was analyzed in patients classified according to prespecified PD-L1 expression cutoffs: PD-L1 high (if &gt;1% of the tumor area contained tumor-associated immune cells, ≥25% of tumor cells or ≥25% of immune cells stained for PD-L1; if ≤1% of the tumor area contained immune cells, ≥25% of tumor cells or 100% of immune cells stained for PD-L1) and PD-L1 low/negative (did not meet criteria for PD-L1 high). Results.— The assay met all predefined acceptance criteria for sensitivity, specificity, and precision. Interreader and intrareader precision overall agreement were 93.0% and 92.4%, respectively. For intraday reproducibility and interday precision, overall agreement was 99.2% and 100%, respectively. Interlaboratory overall agreement was 92.6%. In study CD-ON-MEDI4736-1108, durvalumab demonstrated clinical activity and durable responses in both PD-L1–high and PD-L1–low/negative subgroups, although objective response rates tended to be higher in the PD-L1–high subgroup than in the PD-L1–low/negative subgroup. Conclusions.— Determination of PD-L1 expression in urothelial carcinoma patients using the Ventana PD-L1 (SP263) assay was precise, highly reproducible, and clinically relevant.

scholarly journals Optimal Evaluation of Programmed Death Ligand-1 on Tumor Cells Versus Immune Cells Requires Different Detection Methods

2018 ◽  
Vol 142 (8) ◽  
pp. 982-991 ◽  
Author(s):  
Kelly A. Schats ◽  
Emily A. Van Vré ◽  
Carolien Boeckx ◽  
Martine De Bie ◽  
Dorien M. Schrijvers ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Detection Method ◽  
Death Receptor ◽  
Detection Methods ◽  
Programmed Death Ligand 1 ◽  
Cell Staining ◽  
Programmed Death

Context.— The benefit of programmed death ligand-1 (PD-L1) immunohistochemistry (IHC) as a method to select patients who may benefit from programmed death receptor-1 (PD-1)/PD-L1 immunotherapies remains uncertain in many tumor indications. Objectives.— To compare the commercially available, approved PD-L1 IHC assays (22C3, 28-8, SP142, SP263), specifically identifying the changes in staining output created by altering the detection method. Design.— This pilot study investigates the respective PD-L1 kit assay staining patterns and related scoring of tumor cells and immune cells on lung carcinoma and melanoma. Furthermore, the influence of the detection method (platform and related reagents) on PD-L1 antibody performance is studied. Results.— The SP142 kit reveals more immune cell staining but less tumor cell staining than the other PD-L1 kits. Alternatively, the 22C3 and 28-8 kits show good tumor cell sensitivity, but less pronounced immune cell staining, even in tonsil. Tumor cell staining by the SP263 kit is comparable to that of 22C3 and 28-8 kits, while immune cell staining is better. Strikingly, the selection of the detection method has a major impact on the sensitivity of the assay for PD-L1 detection per cell type. Switching the detection method of the kits could largely circumvent the observed staining differences. Conclusions.— The diverse sensitivities caused by the choice of the detection method should be taken into consideration when selecting PD-L1 kits or developing PD-L1 IHC laboratory-developed tests. When using alternative kits or laboratory-developed tests, it is strongly recommended to reestablish their clinical utility per therapeutic agent or compare them with the original kit.

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 &lt; .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 &lt; .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 Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC

2019 ◽  
Vol 14 (4) ◽  
pp. 628-640 ◽  
Author(s):  
Karolina Edlund ◽  
Katrin Madjar ◽  
Johanna S.M. Mattsson ◽  
Dijana Djureinovic ◽  
Cecilia Lindskog ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Prognostic Impact ◽  
Immune Cell Infiltration ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

scholarly journals In-Silico Analysis of The Correlation Between PD-L1 and Pro-Inflammatory Type Interleukins and The Distribution of Their Potential Primary Sources in KRAS-Mutated Non-Small Cell Lung Carcinoma

Acta Medica ◽  
2021 ◽  
pp. 1-8
Author(s):  
Nese Unver
Keyword(s):  
Lung Cancer ◽  
Dendritic Cells ◽  
Cancer Cells ◽  
Immune Cells ◽  
Small Cell ◽  
Interleukin 12 ◽  
Small Cell Lung ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Interleukin 23

Objective: Non-Small Cell Lung Cancer has a high incidence and great clinical importance as the cancer subtype with the highest mortality. It is necessary to investigate cytokines associated with the Programmed death-ligand 1, one of the immunotherapeutic target molecules, in KRas mutant lung cancer cells. Materials and Methods: In this study, the expression of Programmed death-ligand 1 as well as pro-inflammatory interleukins was evaluated in 44 lung cancer cell lines harboring KRas mutations and RNAseq expression data of lung adenocarcinoma patients and correlation analyses were performed. Macrophages and dendritic cells, the major immune cells associated with Interleukin-1, Interleukin-6, Interleukin-12 and Interleukin-23, were also evaluated. Results: In KRas mutant lung cancer cells and lung adenocarcinoma tissues, expression of cytokines Interleukin-1A, Interleukin-6, Interleukin-12 and Interleukin-23 showed a positive correlation with Programmed death-ligand 1 expression (p≤0.05). The quantity of M1 macrophages and dendritic cells, both of which are cytokine-producing immune cells, is less in KRas mutant lung cancer tissues than non-mutants. Conclusion: Detailed studies in clinical samples, especially in blood, primary, and metastatic tissues, will help to create and validate cytokine panels that can be used in therapeutic targeting of KRas mutant subtype lung cancer with high Programmed death-ligand 1 expression.

scholarly journals BRAFV600E in Papillary Thyroid Carcinoma Is Associated with Increased Programmed Death Ligand 1 Expression and Suppressive Immune Cell Infiltration

Thyroid ◽  
2014 ◽  
Vol 24 (9) ◽  
pp. 1385-1393 ◽  
Author(s):  
Trevor E. Angell ◽  
Melissa G. Lechner ◽  
Julie K. Jang ◽  
Adrian J. Correa ◽  
Jonathan S. LoPresti ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Papillary Thyroid ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

Expression of Programmed Death-Ligand 1 in Laryngeal Carcinoma and its Effects on Immune Cell Subgroup Infiltration

2018 ◽  
Vol 25 (4) ◽  
pp. 1437-1443 ◽  
Author(s):  
Dan Yu ◽  
Jinzhang Cheng ◽  
Kai Xue ◽  
Xue Zhao ◽  
Lianji Wen ◽  
...  
Keyword(s):  
Laryngeal Carcinoma ◽  
Immune Cell ◽  
Programmed Death Ligand 1 ◽  
Programmed Death
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