scholarly journals Trends in the Research Into Immune Checkpoint Blockade by Anti-PD1/PDL1 Antibodies in Cancer Immunotherapy: A Bibliometric Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Yiting Sun ◽  
Liqing Jiang ◽  
Ti Wen ◽  
Xiaoyu Guo ◽  
Xinye Shao ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Molecular Mechanisms ◽  
Randomized Clinical Trials ◽  
Tumor Regression ◽  
Meta Analysis ◽  
Death Receptor ◽  
Bibliometric Study ◽  
Immune Checkpoints ◽  
Knowledge Map ◽  
Programmed Death

The programmed death receptor 1 (PD1) and its ligand programmed death receptor ligand 1 (PDL1) are the most widely used immune checkpoints in cancer immunotherapy. The related literature shows the explosive growth trends due to the promising outcomes of tumor regression. The present study aimed to provide a comprehensive bibliometric analysis of the literature on anti-PD1/PDL1 from three perspectives including molecular mechanisms, randomized clinical trials (RCT), and meta-analysis, thus producing a knowledge map reflecting the status of the research, its historical evolution, and developmental trends in related research from 2000 to 2020. We included 11,971, 191, and 335 documents from the Web of Science Core Collection database, respectively, and adopted various bibliometric methods and techniques thereto. The study revealed the major research themes and emergent hotspots based on literature and citation data and outlined the top contributors in terms of journals and countries. The co-occurrence overlay of keywords and terms pertaining to the PD1/PDL1 molecule reflected the progress from the discovery of the PD1/PDL1 molecule to the clinical application of anti-PD1/PDL1. Immune-related adverse events (irAEs) formed a unique cluster in the term co-occurrence analysis of meta-analysis. The historical direct citation network of RCT indicated the development and transformation of cancers and therapy strategies. irAEs and the strategies of combination therapy might become a future focus of research in this cognate area. In summary, the bibliometric study provides a general overview of the landscape on anti-PD1/PDL1 research, allowing researchers to identify the potential opportunities and challenges therein.

scholarly journals A bi-adjuvant nanovaccine that potentiates immunogenicity of neoantigen for combination immunotherapy of colorectal cancer

2020 ◽  
Vol 6 (12) ◽  
pp. eaaw6071 ◽  
Author(s):  
Qianqian Ni ◽  
Fuwu Zhang ◽  
Yijing Liu ◽  
Zhantong Wang ◽  
Guocan Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Immunotherapy ◽  
Death Receptor ◽  
Therapy Response ◽  
Complete Regression ◽  
Combination Immunotherapy ◽  
Toll Like Receptor ◽  
Physical Loading ◽  
Programmed Death ◽  
Personalized Cancer

Neoantigen vaccines have been enthusiastically pursued for personalized cancer immunotherapy while vast majority of neoantigens have no or low immunogenicity. Here, a bi-adjuvant neoantigen nanovaccine (banNV) that codelivered a peptide neoantigen (Adpgk) with two adjuvants [Toll-like receptor (TLR) 7/8 agonist R848 and TLR9 agonist CpG] was developed for potent cancer immunotherapy. Specifically, banNVs were prepared by a nanotemplated synthesis of concatemer CpG, nanocondensation with cationic polypeptides, and then physical loading with hydrophobic R848 and Adpgk. The immunogenicity of the neoantigen was profoundly potentiated by efficient codelivery of neoantigen and dual synergistic adjuvants, which is accompanied by reduced acute systemic toxicity. BanNVs sensitized immune checkpoint programmed death receptor 1 (PD-1) on T cells, therefore, a combination of banNVs with aPD-1 conspicuously induced the therapy response and led to complete regression of 70% neoantigen-specific tumors without recurrence. We conclude that banNVs are promising to optimize personalized therapeutic neoantigen vaccines for cancer immunotherapy.

scholarly journals Development of cancer immunotherapy based on PD-1/PD-L1 pathway blockade

RSC Advances ◽  
2019 ◽  
Vol 9 (58) ◽  
pp. 33903-33911 ◽  
Author(s):  
Min Zhang ◽  
Kehai Liu ◽  
Mingfu Wang
Keyword(s):  
Side Effects ◽  
Cancer Immunotherapy ◽  
Response Rate ◽  
Death Receptor ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

The possible reasons that caused low response rate and severe side effects of programmed death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade therapy and corresponding strategies.

scholarly journals Predictive biomarkers of inhibitors immune checkpoints therapy in malignant tumors

2021 ◽  
Vol 8 (2) ◽  
pp. 73-83
Author(s):  
M. V. Kiselevsky ◽  
I. V. Samoylenko ◽  
O. V. Zharkova ◽  
N. V. Ziganshina ◽  
A. A. Petkevich ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Predictive Biomarkers ◽  
Peripheral Blood Lymphocytes ◽  
Immune Checkpoints ◽  
Russian Science ◽  
Programmed Death ◽  
Number Of Patients ◽  
Russian Science Citation Index

Immune checkpoint inhibitors (ICT) therapy is a successful immunotherapy (IT) strategy that is quite effective in a number of patients with non-small cell lung cancer, melanoma, bladder cancer, breast cancer and others. Nevertheless, there is a need in predictive markers for ICT therapy for personalized IT as far as there is a large group of patients, the proportion of which varies depending on the tumor, who do not have a clinical response to such therapy. The review summarizes the theoretical aspects and results of clinical trials dedicated to various clinical efficiency predictor using modern databases. As a result of the analysis it is established that the main candidates for the role of such markers are tumor infiltrating lymphocytes and their subpopulations, peripheral blood lymphocytes (PBL) and their subpopulations. PD1 (programmed death receptor 1) and PDL1 (programmed death receptor ligand 1) expression in tumor tissue can also be important for predicting IT efficiency. The most promising predictive biomarker meaning the most clinically relevant is a combination of the PBL subpopulations study and PD1 and PDL1 expression on the tumor cells.PubMed, Scopus, Web of Science, eLibrary, Russian Science Citation Index databases were searched for the available appropriate literature reports. The authors included 82 in the given review.

scholarly journals Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II—The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer

2017 ◽  
Vol 142 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Esmeralda Celia Marginean ◽  
Barbara Melosky
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Microsatellite Instability ◽  
Therapeutic Potential ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Immune Checkpoints ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

Context.— The world of oncology has changed dramatically in the past few years with the introduction of checkpoint inhibitors and immunotherapy. The promising findings of a small, phase 2 clinical trial that led to the US Food and Drug Administration breakthrough designation and approval of the anti–programmed death receptor-1 (PD-1) drug pembrolizumab (Keytruda, Merck, Kenilworth, New Jersey) to treat metastatic/refractory microsatellite instability–high colorectal cancer (CRC) has significantly boosted interest in immunomodulatory therapies in microsatellite instability–high CRC. Objectives.— To review the immune response to cancer and the role of immune checkpoints, focusing on the technical and interpretation challenges of PD-1/programmed death ligand-1 (PD-L1) testing by pathologists and the clinical implications of the test and the therapeutic potential of treating CRC with checkpoint inhibitors. Data Sources.— A PubMed review was performed of articles pertaining to CRC, microsatellite instability and mismatch repair systems, molecular classification, immune response, PD-1/PD-L1, and immunotherapy. Conclusions.— Exciting success with anti–PD-1/PD-L1 and anticytotoxic T-lymphocyte–associated protein 4 (CTLA4) checkpoint inhibitors has already been reported in melanoma and in lung and renal carcinomas. Recently, microsatellite instability–high CRCs, expressing PD-L1 by immunohistochemistry, regardless of the level of that PD-L1 expression, appeared to respond to checkpoint blockades with anti–PD-1 or anti–PD-L1 agents, whereas microsatellite-stable tumors were much less responsive. With microsatellite instability routinely tested by most centers, studies that include larger cohorts are required to study the predictive role of PD-1/PD-L1 expression in microsatellite instability–high CRC, to assess which immunohistochemistry antibodies to use, to refine the scoring criteria, and to critically analyze the interpretation pitfalls.

scholarly journals Defining tumor resistance to PD-1 pathway blockade: recommendations from the first meeting of the SITC Immunotherapy Resistance Taskforce

2020 ◽  
Vol 8 (1) ◽  
pp. e000398 ◽  
Author(s):  
Harriet M. Kluger ◽  
Hussein A. Tawbi ◽  
Maria L. Ascierto ◽  
Michaela Bowden ◽  
Margaret K. Callahan ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Unmet Need ◽  
Death Receptor ◽  
Clinical Trial Design ◽  
Standard Of Care ◽  
Tumor Resistance ◽  
Primary Resistance ◽  
New Agents ◽  
Secondary Resistance ◽  
Programmed Death

As the field of cancer immunotherapy continues to advance at a fast pace, treatment approaches and drug development are evolving rapidly to maximize patient benefit. New agents are commonly evaluated for activity in patients who had previously received a programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor as standard of care or in an investigational study. However, because of the kinetics and patterns of response to PD-1/PD-L1 blockade, and the lack of consistency in the clinical definitions of resistance to therapy, the design of clinical trials of new agents and interpretation of results remains an important challenge. To address this unmet need, the Society for Immunotherapy of Cancer convened a multistakeholder taskforce—consisting of experts in cancer immunotherapy from academia, industry, and government—to generate consensus clinical definitions for resistance to PD-(L)1 inhibitors in three distinct scenarios: primary resistance, secondary resistance, and progression after treatment discontinuation. The taskforce generated consensus on several key issues such as the timeframes that delineate each type of resistance, the necessity for confirmatory scans, and identified caveats for each specific resistance classification. The goal of this effort is to provide guidance for clinical trial design and to support analyses of emerging molecular and cellular data surrounding mechanisms of resistance.

scholarly journals Interaction between Immunotherapy and Radiotherapy

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Yasemin Benderli Cihan
Keyword(s):  
Vascular Endothelial Cells ◽  
Transmembrane Protein ◽  
Death Receptor ◽  
Predictive Biomarkers ◽  
Immune Checkpoints ◽  
Myeloid Dendritic Cells ◽  
Activated T Cells ◽  
Lung Cancers ◽  
Therapeutic Modalities ◽  
Programmed Death

In recent years, treatment methods on immune checkpoints have emerged as promising novel therapeutic modalities against cancer as a result of studies focusing on elucidation of immune micro-environment. Immunotherapy has now become an established treatment in some cancers. [1-2] This has led the need for investigation of biomarkers which allow determining effectiveness of immunotherapies and patient groups which will most benefit from these therapies. In previous studies, it was suggested that programmed death receptor-1 (PD-1) and programmed death ligand-1 (PD-L1) expressions could be predictive biomarkers in cancers. PD-1 is a transmembrane protein present in macrophages, myeloid dendritic cells, B cells, epithelial cells and vascular endothelial cells, which limits and inhibits immunological activation in activated T cells. Blocking PD-1/PD-L1 interaction promises hope in the cancer treatment.  In clinical studies, it was shown that targeted PD-1/PD-L1 therapy alone or in combination with other modalities is beneficial in advanced cancers with aggressive behavior. It was shown that overexpression of PD-1 present in tumoral micro-environment is associated to poor prognosis in gastric cancer, breast cancer, ovarian cancer, kidney, pancreas and lung cancers and in melanoma. [1-5]

scholarly journals Comparative efficacy of treatments for previously treated patients with advanced esophageal and esophagogastric junction cancer: A network meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252751
Author(s):  
Shuiyu Lin ◽  
Tingting Liu ◽  
Jun Chen ◽  
Guang Li ◽  
Jun Dang
Keyword(s):  
Esophagogastric Junction ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Death Receptor ◽  
Cochrane Library ◽  
Randomized Controlled ◽  
Programmed Death ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Phase Ii And Iii

Background It remains unclear which treatment is the most effective for previously treated patients with advanced esophageal and esophagogastric junction (EGJ) cancer. We conducted a network meta-analysis to address this important issue. Methods PubMed, Embase, Cochrane Library, and Web of Science databases were searched for relevant phase II and III randomized controlled trials (RCTs). Overall survival (OS) was the primary outcome of interest, which was reported as hazard ratio (HR) and 95% confidence intervals (CIs). Results Sixteen RCTs involving 3372 patients and evaluating 15 treatments were included in this network meta-analysis. Ramucirumab+chemotherapy (CT) (HR = 0.52, 95% CI: 0.35–0.77) and use of programmed death receptor 1 (PD-1) inhibitors, including camrelizumab (HR = 0.71, 95% CI: 0.57–0.88), sintilimab (HR = 0.70, 95% CI: 0.50–0.98), nivolumab (HR = 0.76, 95% CI: 0.62–0.94), and pembrolizumab (HR = 0.84, 95% CI: 0.72–0.98), conferred better OS than CT; however, this OS benefit was not observed for PD-L1 inhibitor (avelumab) and other target agents (trastuzumab, everolimus, gefitinib, and anlotinib). In subgroup analysis, ramucirumab+CT and pembrolizumab showed significant improvement in OS, when compared to CT, in esophageal/EGJ adenocarcinoma (AC) cases; moreover, all PD-1 inhibitors had significant OS advantage over CT in treating esophageal squamous cell carcinoma (SCC). Based on treatment ranking in terms of OS, ramucirumab+CT and camrelizumab were ranked the best treatments for patients with AC and SCC, respectively. Conclusions Ramucirumab+CT and PD-1 inhibitors were superior to CT for previously treated cases of advanced esophageal/EGJ cancer. Ramucirumab+CT seemed to be the most effective treatment in patients with esophageal/EGJ AC, while use of PD-1 inhibitors, especially camrelizumab, was likely to be the optimal treatment in patients with esophageal SCC.

Acute kidney injury in patients treated with anti-programmed death receptor-1 for advanced melanoma: a real-life study in a single-centre cohort

2020 ◽  
Author(s):  
Claire Stein ◽  
Stéphane Burtey ◽  
Julien Mancini ◽  
Marion Pelletier ◽  
Marion Sallée ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Real Life ◽  
Death Receptor ◽  
Kidney Injury ◽  
Advanced Melanoma ◽  
Immune Checkpoints ◽  
Programmed Death

Abstract Background Immune checkpoints inhibitors have transformed the prognosis of advanced melanoma but are associated with immune-related adverse events (irAEs). We evaluated the incidence, risk factors and causes of acute kidney injury (AKI) in a monocentric real-life cohort of patients treated with anti-programmed death receptor-1 (anti-PD1) antibodies for advanced melanoma. Methods Retrospective collection of medical charts and comprehensive analysis of lab results from patients treated with nivolumab or pembrolizumab for advanced melanoma between 2014 and 2018 was carried out. AKI was defined by Kidney Disease Improving Global Outcomes criteria, and causes were determined by chart review. Overall survival, survival without AKI and impact of AKI on survival were analysed. Risk factors for death and for AKI were identified. Results Two hundred and thirty-nine patients were included. Forty-one (17%) had at least one episode of AKI. Independent risk factors for AKI were treatment with renin–angiotensin–aldosterone system inhibitors (RAASi), pre-existing chronic kidney disease (CKD) and cumulated doses of anti-PD1. The main cause of AKI was prerenal, and only eight patients (3.3%) developed acute interstitial nephritis; 8% of patients developed CKD. The median overall survival was 13.4 months and was not affected by AKI. In multivariate analysis, the overall mortality was lower in overweight and obese patients and higher in patients treated with proton-pump inhibitors (PPI) or corticosteroids. Conclusions AKI is common in patients treated with anti-PD1 for advanced melanoma but is mostly prerenal and favoured by the use of RAASi; renal irAE is rare. PPI and corticosteroids were associated with poor survival in this population, while overweight/obesity was protective.

Meta-Analysis of PD-L1 Expression As a Predictor of Survival After Checkpoint Blockade

2020 ◽  
pp. 1196-1206
Author(s):  
Andrea Arfè ◽  
Geoffrey Fell ◽  
Brian Alexander ◽  
Mark M. Awad ◽  
Scott J. Rodig ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Death Receptor ◽  
Specific Treatment ◽  
Survival Times ◽  
Individual Level ◽  
Level Data ◽  
Death Receptor Ligand ◽  
Standard Designs

PURPOSE Programmed cell death receptor ligand 1 (PD-L1) expression is the most studied biomarker to predict the efficacy of immune checkpoint inhibitors (ICIs), but its clinical significance is controversial. We estimated the distribution of PD-L1 expression scores (ie, tumor proportion score or combined proportion score) and the relationship between PD-L1 levels and ICIs’ impact on overall survival (OS). METHODS We reconstructed, pooled, and analyzed individual-level data on 7,617 patients with cancer from 14 randomized clinical trials. The effects of ICIs were quantified using differences in 24-month restricted mean survival times (ΔRMSTs; ie, the increase in life expectancy truncated at 2 years associated with ICI therapy). In a simulation study, we compared standard randomized clinical trial designs with a trial design that leverages meta-analytic results like ours. RESULTS Approximately 93% of patients had a PD-L1 expression ≤ 5% (66% of patients) or > 50% (27% of patients). OS improves with ICIs regardless of PD-L1 expression level, which predicts the benefits’ magnitude. For patients with non–small-cell lung cancer (NSCLC), ΔRMSTs ranged from 1.4 months (95% probability interval [PI], 0.7 to 2.2 months) for PD-L1 expression ≤ 1% to 4.1 months (95% PI, 3.2 to 5.2 months) for PD-L1 expression > 80%. For patients with non-NSCLC tumors, ΔRMSTs ranged from 0.8 months (95% PI, −0.1 to 1.7 months) to 2.3 months (95% PI, 1.3 to 4.4 months), again for PD-L1 expression levels of ≤ 1% and > 80%, respectively. Simulations suggested that designs tailored to meta-analytic results can detect the effects of ICIs in PD-L1 subgroups with higher probability (> 15%) than standard designs. CONCLUSION The practice of dichotomizing the range of PD-L1 expression scores is inadequate for patient stratification. Meta-analytic estimates of the distribution of PD-L1 scores and subgroup-specific treatment effects can improve the designs of future trials of ICIs.

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