scholarly journals Statins Decrease Programmed Death-Ligand 1 (PD-L1) by Inhibiting AKT and β-Catenin Signaling

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2488
Author(s):  
Woo-Jin Lim ◽  
Mingyu Lee ◽  
Yerin Oh ◽  
Xue-Quan Fang ◽  
Sujin Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
De Novo ◽  
Antibody Therapy ◽  
Programmed Death Ligand 1 ◽  
Cancer Models ◽  
Programmed Death ◽  
Previously Treated ◽  
Cell Death Protein ◽  
Mouse Cancer Models

Retrospective observational studies have reported that statins improve clinical outcomes in patients previously treated with programmed cell death protein 1 (PD-1)-targeting monoclonal antibodies for malignant pleural mesothelioma (MPM) and advanced non-small cell lung cancer (NSCLC). In multiple mouse cancer models, de novo synthesis of mevalonate and cholesterol inhibitors was found to synergize with anti-PD-1 antibody therapy. In the present study, we investigated whether statins affect programmed death-ligand 1 (PD-L1) expression in cancer cells. Four statins, namely simvastatin, atorvastatin, lovastatin, and fluvastatin, decreased PD-L1 expression in melanoma and lung cancer cells. In addition, we found that AKT and β-catenin signaling involved PD-L1 suppression by statins. Our cellular and molecular studies provide inspiring evidence for extending the clinical evaluation of statins for use in combination with immune checkpoint inhibitor-based cancer therapy.

Licochalcone A inhibits interferon-gamma-induced programmed death-ligand 1 in lung cancer cells

Phytomedicine ◽  
2021 ◽  
Vol 80 ◽  
pp. 153394
Author(s):  
Luo-Wei Yuan ◽  
Xiao-Ming Jiang ◽  
Yu-Lian Xu ◽  
Mu-Yang Huang ◽  
Yu-Chi Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Interferon Gamma ◽  
Lung Cancer Cells ◽  
Programmed Death Ligand 1 ◽  
Licochalcone A ◽  
Programmed Death

scholarly journals KEYNOTE-025: Phase 1b study of pembrolizumab in Japanese patients with previously treated programmed death ligand 1-positive advanced non-small-cell lung cancer

2019 ◽  
Vol 110 (3) ◽  
pp. 1012-1020 ◽  
Author(s):  
Makoto Nishio ◽  
Toshiaki Takahashi ◽  
Hiroshige Yoshioka ◽  
Kazuhiko Nakagawa ◽  
Tatsuro Fukuhara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Japanese Patients ◽  
Small Cell ◽  
Small Cell Lung ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Previously Treated ◽  
Phase 1B

scholarly journals Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study

2020 ◽  
Vol 38 (14) ◽  
pp. 1580-1590 ◽  
Author(s):  
Roy S. Herbst ◽  
Edward B. Garon ◽  
Dong-Wan Kim ◽  
Byoung Chul Cho ◽  
Jose L. Perez-Gracia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell ◽  
Small Cell Lung ◽  
Long Term Outcomes ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Previously Treated ◽  
Grade 3

PURPOSE In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in previously treated, programmed death-ligand 1 (PD-L1)‒expressing advanced non‒small-cell lung cancer (NSCLC) in patients with a tumor proportion score (TPS) ≥ 50% and ≥ 1%. We report KEYNOTE-010 long-term outcomes, including after 35 cycles/2 years or second-course pembrolizumab. METHODS Of 1,033 patients randomly assigned (intention to treat), 690 received up to 35 cycles/2 years of pembrolizumab 2 mg/kg (n = 344) or 10 mg/kg (n = 346) every 3 weeks, and 343 received docetaxel 75 mg/m2 every 3 weeks. Eligible patients with disease progression after 35 cycles/2 years of pembrolizumab could receive second-course treatment (up to 17 cycles). Pembrolizumab doses were pooled because no between-dose difference was observed at primary analysis. RESULTS Pembrolizumab continued to improve OS over docetaxel in the PD-L1 TPS ≥ 50% and ≥ 1% groups (hazard ratio [HR], 0.53; 95% CI, 0.42 to 0.66; P < .00001; and HR, 0.69; 95% CI, 0.60 to 0.80; P < .00001, respectively) after a 42.6-month (range, 35.2-53.2 months) median follow-up. Estimated 36-month OS rates were 34.5% versus 12.7% and 22.9% versus 11.0%, respectively. Grade 3-5 treatment-related adverse events occurred in 16% versus 37% of patients, respectively. Seventy-nine of 690 patients completed 35 cycles/2 years of pembrolizumab; 12-month OS and progression-free survival rates after completing treatment were 98.7% (95% CI, 91.1% to 99.8%) and 72.5% (95% CI, 59.9% to 81.8%), respectively. Seventy-five patients (95%) had objective response (RECIST v1.1, blinded independent central review) and 48 (64%) had ongoing response. Grade 3-5 treatment-related adverse events occurred in 17.7% of patients. Fourteen patients received second-course pembrolizumab: 5 completed 17 cycles, 6 (43%) had partial response, and 5 (36%) had stable disease. CONCLUSION Pembrolizumab provided long-term OS benefit over docetaxel, with manageable safety, durable responses among patients receiving 2 years of treatment, and disease control with second-course treatment, further supporting pembrolizumab for previously treated, PD-L1‒expressing advanced NSCLC.

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 Therapy-induced E-cadherin downregulation alters expression of programmed death ligand-1 in lung cancer cells

Lung Cancer ◽  
2017 ◽  
Vol 109 ◽  
pp. 1-8 ◽  
Author(s):  
Kenichi Suda ◽  
Leslie Rozeboom ◽  
Christopher J. Rivard ◽  
Hui Yu ◽  
Kim Ellison ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
E Cadherin

scholarly journals Comparison of programmed death-ligand 1 (PD-L1) immunostain for nonsmall cell lung carcinoma between paired cytological and surgical specimens

CytoJournal ◽  
2018 ◽  
Vol 15 ◽  
pp. 29 ◽  
Author(s):  
Huihong Xu ◽  
Laura Bratton ◽  
Michael Nead ◽  
Donna Russell ◽  
Zhongren Zhou
Keyword(s):  
Lung Cancer ◽  
Tumor Cells ◽  
Lung Squamous Cell Carcinoma ◽  
Inflammatory Cells ◽  
Cancer Tissue ◽  
Cell Lung Carcinoma ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Cell Death Protein ◽  
Higher Sensitivity

Background: programmed death-ligand 1 (PD-L1) is a ligand for the inhibitory programmed cell death protein 1 (PD-L1), which are targeted by several anti-PD-1 and PD-L1 drugs for lung cancer treatment. In clinical practice, many lung cancer cases only have cytology samples available to test PD-L1. Our current study compared the PD-L1 immunohistochemistry (IHC) between paired cytological and surgical samples. Materials and Methods: Formalin-fixed lung cancer tissue microarray and paired cell blocks and surgical specimens from the same patients with a confirmed diagnosis of lung squamous cell carcinoma (SCC, n = 29) and adenocarcinoma (AC, n = 23) were sectioned for PD-L1 IHC. Results: PD-L1 was expressed on tumor cells in 16 of 29 (55%) SCC surgical specimens and 18 of 29 (62%) paired cytologic specimens with 83% matched immunostains. PD-L1 was expressed on tumor cells in 13 of 23 (57%) AC surgical specimens and in 17 of 23 (74%) paired cytologic specimens with 79% matched immunostains. The PD-L1 was expressed on inflammatory cells in 20 of 23 (87%) AC surgical specimens and in 15 of 23 (65%) paired cytologic specimens with 70% matched immunostains. The PD-L1 was expressed on inflammatory cells in 18 of 29 (62%) SCC surgical specimens and in 12 of 29 (41%) paired cytologic specimens with 79% matched immunostains. Conclusions: PD-L1 immunostain in cytology samples matched very well with paired surgical samples in both SCC and AC cases. The cytologic samples present slightly higher sensitivity for PD-L1 immunostain on tumor cells as compared to surgical biopsies.

scholarly journals Osimertinib (AZD9291) decreases programmed death ligand-1 in EGFR-mutated non-small cell lung cancer cells

2017 ◽  
Vol 38 (11) ◽  
pp. 1512-1520 ◽  
Author(s):  
Xiao-Ming Jiang ◽  
Yu-Lian Xu ◽  
Mu-Yang Huang ◽  
Le-Le Zhang ◽  
Min-Xia Su ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Egfr Mutated
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