scholarly journals The prognostic impact of programmed cell death 1 and its ligand and the correlation with epithelial-mesenchymal transition in thymic carcinoma

2019 ◽  
Vol 8 (1) ◽  
pp. 216-226 ◽  
Author(s):  
Soichiro Funaki ◽  
Yasushi Shintani ◽  
Eriko Fukui ◽  
Yoko Yamamoto ◽  
Ryu Kanzaki ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Thymic Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Prognostic Impact ◽  
Mesenchymal Transition ◽  
Programmed Cell Death 1

scholarly journals Mutation Ensemble for Response to Programmed Cell Death 1 Inhibition in Thymic Carcinoma

2018 ◽  
Vol 13 (8) ◽  
pp. e150-e152 ◽  
Author(s):  
Hyun-Sung Lee ◽  
Cynthia Y. Truong ◽  
Bryan M. Burt
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Thymic Carcinoma ◽  
Programmed Cell Death 1

Prognostic Impact of Programmed Cell Death-1-Positive Cells on Follicular Lymphoma Patients Might Diminish in the Rituximab Era

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2645-2645
Author(s):  
Hiroyuki Takahashi ◽  
Naoto Tomita ◽  
Seiji Sakata ◽  
Chizuko Hashimoto ◽  
Rika Ohshima ◽  
...  
Keyword(s):  
Cell Death ◽  
Prognostic Factors ◽  
T Cell ◽  
Prognostic Factor ◽  
Programmed Cell Death ◽  
Follicular Lymphoma ◽  
Prognostic Impact ◽  
High Tendency ◽  
Programmed Cell Death 1 ◽  
The Impact

Abstract Abstract 2645 Background Programmed cell death-1 (PD-1) is involved in one of the inhibitory pathways of the B7-cluster of differentiation (CD) 28 family; this pathway is known to be involved in the attenuation of T cell responses and promotion of T cell tolerance. PD-1 is known to negatively regulate T cell receptor-mediated proliferation and cytokine production, lead to alternation in the tumor microenvironment. Carreas et al. (J Clin Oncol. 2009; 27: 1470–1476) examined 100 follicular lymphoma (FL) patients and reported better prognosis in the group that had high levels of PD-1-positive cells. In contrast, in the study performed by Richendollar et al. (Human Pathol. 2011; 42: 552–557), which involved 91 FL patients, high levels of PD-1-positive cells were found to have a poor prognostic impact. Although these studies have shown that high levels of PD-1-positive cells in FL patients influence their prognosis, both studies included patients treated without rituximab, and the prognostic impact of PD-1 positivity in the rituximab-era (R-era) has not yet been elucidated. Materials and methods We retrospectively analyzed data for 91 FL patients uniformly treated by standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy in 5 institutions between 2001 and 2009. The median age of the entire cohort was 58 years (range, 34–85 years), and 46 (51%) of the patients were men. We also collected and examined biopsy specimens for diagnosis with respect to PD-1 positivity. The PD-1-positive cells were counted using computer analysis at the Cancer Institute, Japanese Foundation for Cancer Research. Results The FL grade on diagnosis was grade 1 for 34 (37%) patients, grade 2 for 41 (45%) patients, and grade 3 for 16 (18%) patients. The median positivity for PD-1 staining was 16.0% (range, 0.01–51.9%) and was significantly higher in the high beta-2 microglobulin (B2M; at least 3) group (P = 0.009); the men had a high tendency for PD-1 positivity (P = 0.08). After a median follow-up of 29.1 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 61.1% and 88.6%, respectively. Stage 4 FL at diagnosis (P = 0.02) and bone marrow involvement (P = 0.05) resulted in worse PFS, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2–4 (P = 0.04), high Follicular Lymphoma International Prognostic Index (FLIPI; P = 0.02), B symptoms (P = 0.04), and high B2M levels (P = 0.005) worsened OS. Multivariate analysis showed that age over 60 years (P = 0.04) and high B2M levels (P = 0.07) were prognostic factors for PFS. PD-1 positivity was not found to be a prognostic factor with respect to both PFS and OS. Because the addition of rituximab to therapy regimens has altered the clinical course and prognosis of FL, some new prognostic factors have been proposed, and the impact of known prognostic factors has been changing. Rituximab might also have changed the prognosis of FL patients with high levels of PD-1-positive cells. Conclusion High levels of PD-1-positive cells were not found to be a prognostic factor in this study, indicating that the prognostic impact of PD-1 positivity might be eliminated in the R-era. Disclosures: No relevant conflicts of interest to declare.

PD-L1 expression level in different thymoma stages and thymic carcinoma: a meta-analysis

2020 ◽  
Vol 106 (4) ◽  
pp. 306-311
Author(s):  
Hua-Fei Chen ◽  
Li-Xin Wu ◽  
Xiao-Feng Li ◽  
You-Cai Zhu ◽  
Wei-Wei Pan ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Thymic Carcinoma ◽  
Meta Analysis ◽  
Type A ◽  
Expression Level ◽  
Programmed Cell Death 1 ◽  
Significant Difference ◽  
Cell Death Protein ◽  
Potential Use

Background: The immune checkpoint ligand, programmed cell death 1 ligand 1 (PD-L1), is expressed in various tumors and associated with response to drugs that target programmed cell death protein 1. Previous studies have estimated the level of PD-L1 expression among different stages of thymoma and thymic carcinoma to evaluate its potential use as a diagnostic factor; however, its varying expression level has been problematic. We conducted this meta-analysis of published literature to evaluate PD-L1 expression in thymomas and thymic carcinomas. Methods: We analyzed 12 studies that included 320 patients with type A/AB/B1 thymoma, 225 patients with type B2/B3 thymoma, and 180 patients with thymic carcinoma. Results: No difference in PD-L1 expression level was found between the B2/B3 vs C groups (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.26, 1.76; p = 0.42). However, the heterogeneity was very high ( I2 = 78%), and a significant difference was found between groups A/AB/B1 and B2/B3 (OR, 0.22; 95% CI, 0.12, 0.41; p < 0.001), with a relatively low heterogeneity ( I2 = 55%). Conclusion: PD-L1 positivity might be a useful factor to differentiate type A/AB/B1 thymoma from type B2/B3 and thymic carcinoma. This result might be valuable for potential anti PD-L1 treatment in thymoma and thymic carcinoma.

Prognostic value of programmed death-ligand 1 in solid tumors: A meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19121-e19121
Author(s):  
Jordan L Scott ◽  
Michelle Nadler ◽  
Alexandra Desnoyers ◽  
Fahad Almugbel ◽  
Rouhi Fazelzad ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Solid Tumors ◽  
Early Stage ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Significant Heterogeneity ◽  
Prognostic Impact ◽  
Stage Of Disease ◽  
Programmed Cell Death 1

e19121 Background: The programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) pathway plays a crucial role in cancer immuno-surveillance and is the target of approved immunotherapeutic drugs. Available data suggest a variable prognostic impact of PD-L1 expression in solid tumors. Methods: A systematic literature search of electronic databases identified publications exploring the effect of PD-L1 on overall survival (OS) and/or progression-free survival (PFS). Hazard ratios (HR) were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on disease site, stage of disease, and method of PD-L1 quantification using the Deeks method. Results: One hundred eighty-eight studies comprised of 212,748 patients met the inclusion criteria. PD-L1 expression was associated with worse OS (HR 1.32, 95% confidence interval (CI) 1.25 - 1.38; P < 0.001). There was significant heterogeneity between disease sites (subgroup P = 0.002) with pancreatic, hepatocellular and genitourinary cancers being associated with the highest magnitude of adverse outcome (Table). PD-L1 was also associated with worse overall PFS (HR 1.19, 95% CI 1.09 - 1.30; P < 0.001). Stage of disease did not significantly affect the results (subgroup P = 0.52), nor did the method of quantification (immunohistochemistry or mRNA) (subgroup P = 0.70). Conclusions: High expression of PD-L1 is associated with worse cancer outcomes albeit with significant heterogeneity between disease sites. The effect seems consistent in early stage and metastatic disease and is not sensitive to method of PD-L1 quantification. [Table: see text]

scholarly journals P1.17-013 Prognostic Impact of Programmed Cell Death-1 (PD-1) and PD-Ligand 1 (PD-L1) Expression in Thymic Cancer

2017 ◽  
Vol 12 (11) ◽  
pp. S2065-S2066
Author(s):  
S. Funaki ◽  
Y. Shintani ◽  
N. Ose ◽  
T. Kawamura ◽  
R. Kanzaki ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Prognostic Impact ◽  
Thymic Cancer ◽  
Programmed Cell Death 1
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