scholarly journals The potential prognostic and predictive roles of programmed cell death protein 1 expressed by tumor-infiltrating lymphocytes in solid tumors: a meta-analysis

2018 ◽  
Vol 4 (4) ◽  
pp. 16
Author(s):  
Dong-Yun Zhang ◽  
Rong-Zhi Liu ◽  
Jian-Wei Ku ◽  
Yu-Hong Ma ◽  
Ying-Jie Yi
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Solid Tumors ◽  
Meta Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes ◽  
Cell Death Protein

scholarly journals Tumor-Infiltrating Lymphocytes in Triple Negative Breast Cancer: The Future of Immune Targeting

2016 ◽  
Vol 10s1 ◽  
pp. CMO.S34540 ◽  
Author(s):  
Paula García-Teijido ◽  
María Luque Cabal ◽  
Ignacio Peláez Fernández ◽  
Yolanda Fernández Pérez
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Immune System ◽  
Programmed Cell Death ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumor Infiltrating Lymphocytes ◽  
Immune Checkpoints ◽  
Infiltrating Lymphocytes ◽  
Cell Death Protein

Triple negative breast cancer (TNBC) is a highly heterogeneous tumor. There is increasing evidence of the role of tumor lymphocytic immune infiltrates in this subtype of breast cancer. Robust levels of tumor infiltrating lymphocytes (TILs) have been associated with improved disease-free and overall survival rates in TNBC patients with and without any treatment. Recent efforts have been made to develop a standardized methodology for evaluating TILs. The presence of TILs in the breast tumor microenvironment can also predict responses not only to neoadjuvant but also to adjuvant chemotherapy treatments. High numbers of TILs correlate with increased pathological complete responses (pCR) in TNBC. TILs are prognostic and predictive of response to standard therapies; thus, the immune system appears to play an active role in a subgroup of breast cancer. There is an increasing interest in directly targeting the immune system as part of breast cancer therapy, mainly in patients with TNBC. New immune modulatory agents, including immune checkpoints inhibitors, have shown promising activity in a subgroup of metastatic TNBC. Increased programmed cell death protein 1 ligand (PD-L1) expression on the surface of TNBC provides the rationale for implementing therapeutic strategies targeting the PD-1/PD-L1 axis in TNBC. The programmed cell death protein 1 (PD-1) inhibitor pembrolizumab, and the PD-L1 inhibitor atezolizumab have shown promising results in clinical trials.

scholarly journals Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia: meta-analysis

2018 ◽  
Vol 34 (1) ◽  
pp. 108-117 ◽  
Author(s):  
Sandhya Manohar ◽  
Panagiotis Kompotiatis ◽  
Charat Thongprayoon ◽  
Wisit Cheungpasitporn ◽  
Joerg Herrmann ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Cell Death Protein ◽  
Inhibitor Treatment

scholarly journals Fatal adverse events associated with programmed cell death protein 1 or programmed cell death-ligand 1 monotherapy in cancer

2020 ◽  
Vol 12 ◽  
pp. 175883591989575
Author(s):  
Bin Zhao ◽  
Hong Zhao ◽  
Jiaxin Zhao
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Adverse Events ◽  
Solid Tumors ◽  
Sequential Analysis ◽  
Trial Sequential Analysis ◽  
Tumor Type ◽  
Organ Systems ◽  
Fatal Adverse Events ◽  
Cell Death Protein

Background: The introduction of antibodies targeting programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) into clinical practice has had a revolutionary effect on cancer treatment. However, the incidence and risk of fatal adverse events (FAEs) following PD-1/PD-L1 inhibitor administration are controversial. Methods: We performed a systematic search for randomized controlled trials (RCTs) of PD-1/PD-L1 inhibitors (atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab) in Embase, PubMed, the Cochrane database, and abstracts presented at American Society of Clinical Oncology and European Society of Medical Oncology from inception to July 2018. FAEs were extracted from each study and pooled to calculate overall incidence and odds ratios (ORs). Results: In total, 20 RCTs involving 12,398 patients with solid tumors were included in this study. The overall incidence of FAEs with PD-1/PD-L1 inhibitors was 0.43% [95% confidence interval (CI), 0.25–0.66%]. However, the incidences of FAEs varied significantly by tumor type and median follow-up time. Compared with conventional agents, the application of PD-1/PD-L1 inhibitors significantly reduced the risk of FAEs (OR, 0.56; 95% CI, 0.35–0.89; p = 0.015). Moreover, trial sequential analysis confirmed that our results were solid and reliable; further studies were unlikely to alter this conclusion. FAEs occurred dispersed in major organ systems, with the most common mortalities appearing in the respiratory system (46.2%). Conclusions: Compared with conventional treatment, PD-1/PD-L1 blockade monotherapy is associated with a significantly reduced risk of mortality in patients with solid tumors.

Programmed Cell Death 1 (PD-1) Ligand (PD-L1) Expression in Solid Tumors As a Predictive Biomarker of Benefit From PD-1/PD-L1 Axis Inhibitors: A Systematic Review and Meta-Analysis

2017 ◽  
pp. 1-15 ◽  
Author(s):  
Monica Khunger ◽  
Adrian V. Hernandez ◽  
Vinay Pasupuleti ◽  
Sagar Rakshit ◽  
Nathan A. Pennell ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Solid Tumors ◽  
Immune Cell ◽  
Meta Analysis ◽  
Objective Response ◽  
Small Cell Lung ◽  
Programmed Cell Death 1 ◽  
Tumor Types

Purpose Drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway show significant clinical activity across several tumor types. However, a majority of patients do not respond to these agents. Use of biomarker assays to predict response to these agents is an active area of research; however, the predictive value of PD-L1 immunohistochemistry (IHC) assays is largely inconsistent across clinical trials. In this meta-analysis of clinical trials of PD-1/PD-L1–targeted agents, we evaluate the predictive value of a tumor and tumor-infiltrating immune cell PD-L1 IHC assay as a biomarker for objective response to PD-1/PD-L1 inhibitors. Methods We searched databases (PubMed, Medline, ASCO abstracts, European Society for Medical Oncology abstracts, and Scopus) up until December 2016 for clinical trials using PD-1/PD-L1 inhibitors with reported PD-L1 biomarker data. Objective response rates (primary end point) from all phase I to III trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab in advanced solid tumors were collected. Odds ratios (ORs) for response in PD-L1–positive patients compared with PD-L1–negative patients were calculated using the DerSimonian-Laird random effects model to combine trials. We performed meta-analysis as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results Forty-one distinct trials with 6,664 patients were identified. PD-L1 expression was predictive of favorable response across all tumor types (OR, 2.26; 95% CI, 1.85 to 2.75; P < .001), with the significantly largest effect observed in non–small-cell lung cancer (OR, 2.51; 95% CI, 1.99 to 3.17; P < .001). A subgroup analysis across all non–small-cell lung cancer trials using nivolumab and Dako clone 28-8 (Dako, Carpinteria, CA) IHC antibody assay yielded a significantly higher objective response rate in patients with tumor PD-L1 expression even at the minimum cutoff value of 1% (OR, 2.17; 95% CI, 1.03 to 4.57). Conclusion Our meta-analysis shows that tumor and tumor-infiltrating immune cell PD-L1 overexpression based on IHC is associated with significantly higher response rates to PD-1/PD-L1 axis inhibitors across a range of malignant solid tumors.

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