Response was assessed every 4 cycles using Response Evaluation Criteria in Solid Tumors version 1.1. Here, we showed dysregulation of programmed cell death-ligand 1/programmed cell death 1 (PD-L1/PD-1… Baseline patient and tumor characteristics are given in the Table. However, survival curves of duration of response overlapped between responders with PD-L1 TPS of at least 50% and those with PD-L1 TPS of less than 50% (eFigure 3B in the Supplement). All Rights Reserved.  et al. Close-Up Views of the hPD-1/hPD-L1…, Figure 2. © 2020 American Medical Association. This study was registered at the UMIN Clinical Trials Registry as UMIN000022505. Future studies will need to investigate the evolving PD-L1 genetic complexity in cancer cells.  Clinical significance of PD-L1 and PD-L2 copy number gains in non–small cell lung cancer. , Ikeda Funding/Support: This was an investigator-initiated study supported by Ono Pharma and Bristol-Myers Squibb. Responses among patients with PD-L1 amplification were long lasting, leading to excellent progression-free and overall survival outcomes. Dublin, Oct. 09, 2020 (GLOBE NEWSWIRE) -- The "Programmed Death-Ligand 1 (PD-L1) Non-Small Cell Lung Cancer (NSCLC)-Market Insights, Epidemiology and Market Forecast - 2030" … Meeting abstracts Programmed cell death-1 (PD-1) is a co-inhibitory receptor expressed on lymphoid and non-lymphoid-derived cells that negatively regulates peripheral T-cell responses.  et al; KEYNOTE-024 Investigators.  H.  P, A, Scatterplot depicting the correlation between PD-L1 tumor proportion score and PD-L1 copy number (Spearman ρ = 0.24; 95% CI, 0.10 to 0.37; P < .001). (A) Front-side view.  DS, Koelzer Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2.  MD, Snyder Programmed cell death 1 (PD-1), a member of the B7 receptor family, is an inhibitory receptor expressed on the surface of T cells.  S. Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License. Of these, 155 (79.9%) were men, with a median (range) age of 69 (43-83) years. If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. HHS Second, actual PD-L1 status during nivolumab treatment might not be represented because of the interval between sampling and nivolumab therapy initiation. Identify all potential conflicts of interest that might be relevant to your comment.  K, Earlier assessment of progressive disease before 4 cycles was allowed if progression was suspected.  T, Rizvi  J, Reckamp All Rights Reserved. Not all submitted comments are published. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error.  SM, Lesokhin Understanding the Targeting Mechanisms of Multi-Specific Biologics in Immunotherapy with Multiscale Modeling.  MG, Advani  et al.  Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via, Yoshimura  MR, Monti This multicenter cohort study enrolled 200 patients, of whom 194 had assessable tumors, with advanced or recurrent NSCLC who were treated with nivolumab after progression following prior treatment at 14 institutions in Japan between July 2016 and December 2018.  B, Kim R21 GM087617/GM/NIGMS NIH HHS/United States, R01 GM097082/GM/NIGMS NIH HHS/United States, P41 GM094055/GM/NIGMS NIH HHS/United States, 1P41GM094055/GM/NIGMS NIH HHS/United States, 1R21GM087617/GM/NIGMS NIH HHS/United States, 1R01GM097082/GM/NIGMS NIH HHS/United States, NCI CPTC Antibody Characterization Program. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Accessibility Statement, Figure 1. Partial Least-Squares Discriminant Analysis and Ensemble-Based Flexible Docking of PD-1/PD-L1 Inhibitors: A Pilot Study.  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. , von Elm Blockers of the PD-L1 and PD-1 interaction are an important new anticancer drug class.  Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. , Le Indeed, previously treated patients with NSCLC who had PD-L1 expression of at least 50% had more response to pembrolizumab compared with those with PD-L1 expression between 1% and 50%.3 However, in our study, PD-L1 expression was relatively low (TPS, ≤15%) in 2 of 5 PD-L1–amplified tumors.  DG, Egger  A, Soria  S, Stein  Response to Nivolumab According to Programmed Death Ligand 1 (, Table. All residues important for the interaction are highlighted as sticks. Our website uses cookies to enhance your experience.  DW, Design, Setting, and Participants  The significance of PD-L1 CNGs in the context of ICI therapy was originally highlighted in a previous study showing a high rate (87%) of response to nivolumab, including 17% complete response in heavily pretreated Hodgkin lymphoma32 that usually carries a very low level of TMB,33 given that all tumors analyzed by FISH had an increased PD-L1 gene dosage. Critical revision of the manuscript for important intellectual content: Inoue, Yoshimura, Nishimoto, Inui, Karayama, Fujisawa, Enomoto, Nakamura, Asada, Uto, Fujii, Matsui, Matsuura, Toyoshima, Kusagaya, Matsuda, Kaida, Niwa, Ito, Sugimura.  Nivolumab versus docetaxel in advanced squamous-cell non–small cell lung cancer. , Borghaei To evaluate whether PD-L1 (CD274) copy number gains (CNGs), comprising amplification and polysomy, in pretreatment specimens assessed by fluorescence in situ hybridization are associated with response to nivolumab monotherapy in NSCLC.  T, Okano  et al. …  B, Califano This study reveals the molecular details of the human PD-1/PD-L1 interaction based on an X-ray structure of the complex.  S, Okamoto Data were analyzed from December 2019 to February 2020. With the planned sample size, the ORR would be estimated with the half width of the 95% CI within 15%. (A) Apo-hPD-1.  Pan-cancer immunogenomic perspective on the tumor microenvironment based on PD-L1 and CD8 T-Cell infiltration. , World Medical Association.  PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. , Barrett Waterfall Plot Showing the Best Percentage Change From Baseline, eFigure 6. 2016 May 24;7(21):30323-35. doi: 10.18632/oncotarget.8730.  Nivolumab versus docetaxel in advanced nonsquamous non–small cell lung cancer. . Mol Biosyst.  Atezolizumab versus docetaxel in patients with previously treated non–small cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. , Reck  et al. Epub 2017 Feb 11. Despite being hampered by the low prevalence, this association appears to be more clinically meaningful than selection of patients based on PD-L1 expression at any threshold applied. First, definite conclusions are still precluded because of the small number of patients with PD-L1 amplification. This multicenter cohort study enrolled 200 patients, of whom 194 had assessable tumors, with advanced or recurrent NSCLC who were treated with nivolumab after progression following prior treatment at 14 institutions in Japan between July 2016 and December 2018.  Genomic correlates of response to immune checkpoint blockade. , Green Third, we could not assess TMB and characteristics of the TME, mainly owing to the limited small biopsy samples.  et al. They were not compensated for their time. Within the complex structure, hPD-1 is colored blue and hPD-L1 is colored green; both are shown in stereo view in ribbon representation. The primary end point was the difference in overall response rate (ORR), defined as partial response plus complete response using RECIST version 1.1, according to the PD-L1 copy number status; secondary end points included the differences in progression-free survival (PFS) and overall survival (OS) based on PD-L1 copy number status. Adverse events were graded based on the National Cancer Institute Common Toxicity Criteria version 4.0.  et al.  H, Sanchez-Vega They were not compensated for their time. Customize your JAMA Network experience by selecting one or more topics from the list below.  et al; PACIFIC Investigators.  N, Havel  H, Wooten PD-L1 is a transmembrane protein that belongs to the Ig superfamily consisting of an extracellular N-terminal V domain (IgV) and one C domain (IgC) connected by a short linker.1 H-15 N … Most patients were men (155 [79.9%]) and had a history of smoking (162 [83.5%]), PS 0 or 1 (186 [95.9%]), and stage IV disease (136 [70.6%]). Representative images of fluorescence in situ hybridization analysis of tumors carrying PD-L1 disomy, polysomy, or amplification obtained from patients enrolled in this study (original magnification ×100).  PD-L1 Is upregulated by simultaneous amplification of the, Chen All PD-L1–amplified tumors were adenocarcinomas without EGFR and ALK alterations that developed in male smokers, except for 1 with squamous histology (eTable in the Supplement).  AH, For the other patient with PD-L1 amplification who responded, nivolumab was terminated after 5 cycles because of grade 2 colitis as an adverse effect. Front Immunol. We validated the comparative performance of the E1L3N antibody with the referenced antibodies in immunocytochemistry and IHC (eFigure 2A in the Supplement) and Western blot (eFigure 2B in the Supplement) analyses. Second, a detailed molecular map of the interaction surface is provided, allowing definition of the regions within both interacting partners that may likely be targeted by small molecules. Zak KM, Grudnik P, Magiera K, Dömling A, Dubin G, Holak TA. Regulatory approval of pembrolizumab for treatment of gastric and gastroesophageal junction (G/GEJ) adenocarcinoma required a reproducible scoring method for use of programmed death ligand-1 (PD … Published: September 21, 2020. doi:10.1001/jamanetworkopen.2020.11818. doi:10.1001/jamanetworkopen.2020.11818, Is the copy number status of the programmed death ligand 1 (, In this cohort study of 194 patients with non–small cell lung cancer who were treated with nivolumab monotherapy, the proportion of patients with. PD-L1 and CEP9 signals are shown in red and green, respectively. Terms of Use| hPD-1 and hPD-L1 are represented by blue and green ribbons, respectively. Of these, 155 (79.9%) were men, with a median (range) age of 69 (43-83) years. Among the 200 patients enrolled in this study, 6 patients were excluded due to poor-quality tumor specimens for FISH (5 [83.3%]) or both FISH and IHC (1 [16.7%]), resulting in 194 assessable patients.  A, Tay Epub 2017 Jun 23. Kuang Z, Heng Y, Huang S, Shi T, Chen L, Xu L, Mei H. ACS Omega.  Y, Yoshimura The "Programmed Death-Ligand 1 (PD-L1) Non-Small Cell Lung Cancer (NSCLC)-Market Insights, Epidemiology and Market Forecast - 2030" drug pipelines has been added to … Of note, the 5 PD-L1–amplified tumors exhibited various PD-L1 TPS values, ranging from 4% to 95% (eTable in the Supplement).  JP; STROBE Initiative. Programmed death ligand-1(PD-L1)の発現は、さまざまな癌腫において予後不良因子 であるとの報告がなされてきました。しかし近年、乳癌や悪性黒色腫などにおいて、そ の発言が良好な予後と関 … (A and B) Surface representation of the hPD-L1 binding site of hPD-1.  P, Patients with a PD-L1 TPS of at least 50% had a superior median PFS of 8.1 (95% CI, 2.1-20.9) months compared with that of 2.2 (95% CI, 1.8-3.4) months in patients with a TPS of less than 50% (HR, 0.54; 95% CI, 0.33-0.90; P = .02) (eFigure 7A in the Supplement). Poor outcome with anti-programmed death-ligand 1 (PD-L1) antibody due to poor pharmacokinetic properties in PD-1/PD-L1 blockade-sensitive mouse models.  Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. , Friedman Representative computed tomography scans demonstrating response in a patient with PD-L1–amplified adenocarcinoma are shown in eFigure 4 in the Supplement. Figure 1.  First-line nivolumab plus ipilimumab in advanced non–small-cell lung cancer (CheckMate 568): outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers. , Davoli First, it is shown that the ligand binding to human PD-1 is associated with significant plasticity within the receptor. Nivolumab was repeatedly administered intravenously on day 1 of each 14-day cycle until progressive disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; discontinuation as a result of unacceptable adverse event; or withdrawal of consent.  et al. Concept and design: Inoue, Yoshimura, Inui, Karayama, Matsuda, Sugimura, Suda.  R, Ferrara A total of 6 of the 200 patients were excluded because of poor-quality tumor specimens for the biomarker study, resulting in 194 assessable patients. We calculated that a group of 200 individuals would contain approximately 40 patients with tumors carrying PD-L1 CNGs, based on a prevalence of approximately 20%.22 Although no formal hypothesis testing was planned, we assumed that ORR to nivolumab would be approximately 30% in patients with tumors harboring PD-L1 CNGs. Median (range) age at enrollment was 69 (43-83) years.  MA.  PC, Vandenbroucke  JH,  D, Median (interquartile range) duration of follow-up was 12.6 (5.6-20.4) months.  et al. Targeting programmed death-1 and programmed death-ligand 1 (PD-1/PD-L1) in breast cancer appears increasingly appealing after the success of such an approach in other cancers.  et al. In this cohort study of 194 patients with non–small cell lung cancer who were treated with nivolumab monotherapy, the proportion of patients with PD-L1 amplification who achieved response was 80.0% vs 18.5% among those with PD-L1 polysomy and 17.9% among those with PD-L1 disomy.  AM, Piccioni Median (interquartile range) duration of follow-up was 12.6 (5.6-20.4) months. Produced by tumor to suppress the immune system. This patient received 21 cycles of nivolumab with a PFS of 9.7 months (eTable in the Supplement). Copyright © 2015 Elsevier Ltd. All rights reserved. Programmed death-ligand 1 (PD-L1) protein. Results   K, Inoue  SJ, However, the association of PD-L1 copy number status with TMB remain contradictory,19,34 although PD-L1 expression does not correlate with TMB.12,13,38 In addition, a TMB-independent association between PD-L1 amplification and inflamed TME was reported.25 Further studies are required to elucidate the mechanistic basis for PD-L1 amplification–associated response to ICIs.  H, Paz-Ares Sequential nivolumab was given on day 1 of a 14-day cycle.  MD, Nathanson 2020 Nov 20;23(12):101835. doi: 10.1016/j.isci.2020.101835. Response to Nivolumab According to PD-L1 Protein Expression, eFigure 7. eCollection 2020 Oct 20.  Y, Karayama  et al. Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. 2020;3(9):e2011818. Tumor specimens that contained fewer than 100 tumor cells or showed low quality were excluded from FISH and IHC analyses.  et al. First, it is shown that the ligand binding to human PD-1 is associated with … Pretreatment tumor samples were collected for biomarker evaluation.  D, Margolis When stratified by the presence of PD-L1 CNGs, there was no significant difference in ORR (with CNGs: 28.1%; 95% CI, 13.7%-46.7%; without CNGs: 17.9%; 95% CI, 12.3%-24.7%; P = .22) (Figure 3A). Guzik K, Zak KM, Grudnik P, Magiera K, Musielak B, Törner R, Skalniak L, Dömling A, Dubin G, Holak TA.  et al. Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, play an important role in the maintenance of peripheral tolerance. Progression-Free Survival of Patients Stratified by PD-L1 Protein Expression, eFigure 8. All patients provided written informed consent. To validate the performance of E1L3N, we used positive and negative controls as follows: (1) immunocytochemistry and immunoblot analyses of PD-L1 in PD-L1–negative NCI-H1299 cells in which PD-L1 was exogenously expressed using the p3 × FLAG-CMV-14 vector (Sigma-Aldrich) and (2) IHC of PD-L1 using SignalSlide PD-L1 IHC Controls (Cell Signaling Technology).  Y. Programmed cell death 1 (PD‐1)/PD‐ligand 1(PD‐L1) inhibitors‐related pneumonitis in patients with advanced non–small cell lung cancer Yuxin Sun Department of Pulmonary and Critical … Â, Miao Is the copy number status of the programmed death ligand 1 (PD-L1) gene in non–small cell lung cancer associated with response to nivolumab monotherapy? Response was assessed every 4 cycles (ie, 8 weeks) using RECIST version 1.1 by local investigators. The 28-8 anti–PD-L1 antibody (Abcam) and FLAG-M2 monoclonal antibody (Sigma-Aldrich) were applied for the validation study. Descriptive Statistics for PD-L1 FISH, eFigure 2. Get free access to newly published articles. PFS was defined as the time between the date of the first administration of nivolumab and the date of progression, defined by RECIST version 1.1, or death due to any cause.  N, Hellmann The findings of this study suggest that PD-L1 amplification in non–small cell lung cancer is associated with durable benefit from nivolumab treatment.  et al. The associations of tumor PD-L1 protein expression with PD-L1 copy number and outcomes were also included in the secondary end points. The information will be posted with your response.  B, Andreozzi The median (IQR) follow-up period among 67 patients who were censored was 20.5 (15.4-30.4) months. Targeting the PD-1/PD-L1 immunologic checkpoint with monoclonal antibodies has recently provided breakthrough progress in the treatment of melanoma, non-small cell lung cancer, and other types of cancer.  et al. Overall response rate (ORR) according to the. Author Contributions: Dr Inoue had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conflict of Interest Disclosures: Dr Inui reported receiving grants from Chugai Pharmaceutical Co, Eli Lilly Japan, and MSD KK outside the submitted work. Programmed death ligand 1 (PD-L1) is a critical immune checkpoint ligand whose overexpression on tumor cells provides a mechanism of escape from immune surveillance.  Mutational landscape and sensitivity to immune checkpoint blockers. , Goodman  KS, Lenkiewicz Data were analyzed from December 2019 to February 2020. We aimed to investigate the tissue expression of the immune checkpoint receptor programmed cell death‐1 (PD‐1) and its ligand, programmed death‐ligand 1 (PD‐L1), in PD‐1 …  |  Characteristics of Patients with PD-L1–Amplified Tumors. Corresponding Author: Naoki Inui, MD, PhD, Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan (inui@hama-med.ac.jp). Validation Study of the E1L3N Anti–PD-L1 Antibody, eFigure 4. Immune checkpoint inhibitors (ICIs) targeting programmed death 1 (PD-1) or its ligand (PD-L1) have offered a subset of cancer patients profound and durable survival benefit and transformed the therapeutic landscape of multiple tumor types, particularly in non–small cell lung cancer (NSCLC).1-6 However, the proportion of patients with NSCLC who respond to ICIs is low; response to the anti–PD-1 antibody nivolumab was confirmed in only approximately 20% of patients in the pivotal randomized phase 3 clinical trials.1,2 More troublesome, PD-1/PD-L1 inhibitors can cause immune-related adverse effects7 as well as hyperprogressive disease.8 Therefore, there have been substantial attempts to discover and validate predictive biomarkers to identify patients who may benefit from PD-1/PD-L1 inhibitors by integrating information from tumors, the tumor microenvironment (TME), and the host immune system.9 To date, tumor PD-L1 expression using companion diagnostics is the only approved biomarker to indicate NSCLC patients for PD-1 axis blockade. Robust predictors for response to anti–programmed death 1 and its ligand (PD-1/PD-L1) immunotherapy in non–small cell lung cancer (NSCLC) are not fully characterized. BACKGROUND: Recently, … … Hydrogen bonds are depicted as black dashed lines.  A, Daniel  et al. Overall Survival of Patients Stratified by PD-L1 Protein Expression, eTable. At final database lock on December 9, 2019, the median (interquartile range [IQR]) follow-up was 12.6 (5.6-20.4) months, and 127 patients (65.5%) had died, with study treatment ongoing among 16 patients (8.2%).  F, Waterkamp Response was assessed every 4 cycles using Response Evaluation Criteria in Solid Tumors version 1.1. NIH There was a positive and statistically significant correlation between PD-L1 signals and the PD-L1 to CEP9 ratio (ρ = 0.61; 95% CI, 0.51-0.70; P < .001) (eFigure 1C in the Supplement). All patients received nivolumab monotherapy at a dose of 3 mg/kg; the dosage was changed to a flat 240-mg dose in August 2018, according to the renewed approval by the Japanese Ministry of Health, Labor, and Welfare.  F, Goldberg  Prevalence of PDL1 amplification and preliminary response to immune checkpoint blockade in solid tumors. , Keenan Immunosuppressive drugs have to be taken after organ transplantation, but long-term use of these drugs increases the risks of infection and other serious disorders.  D, Robinson  et al. The Kruskal-Wallis test was used for continuous variables, followed by adjustment using the method of Holm. It is … 細胞質内に ITSM … Programmed death ligand 1(PD-L1) is a critical molecule that inhibits immune responses through its receptor, programmed death-1(PD-1), which is expressed on different immune cells. PD-L1 amplification was defined as a PD-L1 to CEP9 ratio of at least 2.0; polysomy was defined as a mean PD-L1 signal of at least 3.0 and a PD-L1 to CEP9 ratio of less than 2.0; other tumors were defined as disomy.22.  Predictive biomarkers of response for immune checkpoint inhibitors in non-small-cell lung cancer. , Le Additional Contributions: The authors would like to acknowledge patients and their families and Naoko Yoshida and Hisaki Igarashi (Hamamatsu University School of Medicine) for their excellent technical assistance. Programmed cell death 1 ligand 1 (synonym CD274, B7 Homolog 1) ist ein Oberflächenprotein und beteiligt an der Hemmung der Immunantwort.  Tumor and microenvironment evolution during immunotherapy with nivolumab. , Thommen To be eligible for the study, patients for whom nivolumab therapy was planned had to fulfill the following criteria: (1) be aged 18 years or older; (2) have an Eastern Cooperative Oncology Group performance status (PS) of 0 to 2; (3) have histologically proven unresectable stage III or IV or recurrent NSCLC; (4) have progressed following prior treatment; and (5) have available archived formalin-fixed paraffin-embedded tumor for FISH and immunohistochemistry (IHC) analyses of PD-L1. In addition, the benefit observed in patients with PD-L1–amplified tumors irrespective of PD-L1 expression levels suggests other mechanisms that render PD-L1–amplified tumors sensitive to ICIs, including the link with known predictive factors such as TMB. Privacy Policy| OS was defined as the interval from the date of the first administration of nivolumab to the date of death from any cause. This could be partially explained by the finding that group-level and chromosome-level somatic copy number alterations are more negatively associated with cytotoxic immune cell infiltration than the other type of tumor aneuploidy, focal somatic copy number alterations, through a putative mechanism of general gene dosage imbalance rather than the action of specific genes.39 Our definitions of amplification and polysomy are more likely to represent focal and group-level or chromosome-level CNGs, respectively. We thank the Edanz Group for editing a draft of this article. Gly124 Cleft ( L Tyr123-Accommodating Cavity) and CC′ Loop Rearrangement Are Induced by…, Figure 4. This study was conducted in accordance with the Declaration of Helsinki26 and Good Clinical Practice Guidelines, and the protocol was approved by institutional review boards of all participating hospitals. Residues forming the hydrophobic core are colored yellow. BACKGROUND: Programmed cell death 1 (PD-1) receptor engagement on T cells by its ligand programmed cell death ligand 1 (PD-L1) is a key mechanism of immune escape, and antibody …  L, Horn External validation with a larger sample size is warranted to facilitate personalization of PD-1/PD-L1 blockade for patients with NSCLC.  NA, Hellmann  PD-1 blockade induces responses by inhibiting adaptive immune resistance. , Riaz Structure. As a result, median duration of response was not reached (range, 17.7 [ongoing] to 33.7 [ongoing] months) for patients with PD-L1 amplification who responded, which was longer than that among patients with PD-L1 polysomy who responded (14.9 months; 95% CI, 4.6 months to not reached) or those with disomy who responded (16.8 months; 95% CI, 8.1 months to not reached) (eFigure 3A in the Supplement). Recently, a single-nucleotide polymorphism (SNP) in the programmed death ligand 1 (PD-L1) gene has been associated with Graves’ disease (GD) in a Japanese patient cohort. Additional end points were progression-free survival, overall survival, and PD-L1 tumor proportion score (TPS) assessed by immunohistochemistry based on PD-L1 copy number status. Of the 4 patients with PD-L1 amplification who responded to therapy, 3 patients were still receiving study treatment at the final database lock.  Comparison of biomarker modalities for predicting response to PD-1/PD-L1 checkpoint blockade: a systematic review and meta-analysis. , Budczies The interaction between PD … JAMA Network Open. 2020 Oct 1;9(1):1818437. doi: 10.1080/2162402X.2020.1818437. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.27.  |   Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors. , Ansell Herbst These results justify the clinical application of PD-L1 FISH, considering the strong association of PD-L1 amplification with response to PD-1/PD-L1 blockade. eCollection 2020 Dec 18.  JE, Rimm Genomic amplification of this locus is associated with distinct features in multiple tumor types.19-21 We previously reported that PD-L1 copy number gains (CNGs), including amplification and polysomy, as determined by fluorescence in situ hybridization (FISH), were associated with greater PD-L1 expression in NSCLC,22 suggesting that PD-L1 CNGs are responsible for innate immune resistance through constitutive upregulation of PD-L1. Objective  Binding of hPD-L1 Induces Significant…, Figure 1. The number of PD-L1 expression–positive cases at different TPS thresholds were 86 (44.3%) at TPS 1%, 73 (37.6%) at TPS 5%, 61 (31.4%) at TPS 10%, and 24 (12.4%) at TPS 50%. Several other predictors of responsiveness have also been identified, including mismatch repair deficiency,10,11 tumor mutation burden (TMB),12-14 and tumor-infiltrating immune cells.15-17 However, none of these factors appear to be satisfactorily sensitive or specific, even when multiple factors are combined,18 in part owing to technical issues, the dynamic nature of the TME, and the complexity and heterogeneity of cancer cells. 4 Binding of PD-1 to its ligand PD-L1 expressed on … RESEARCH Open Access Prognostic effect of programmed death-ligand 1 (PD-L1) in ovarian cancer: a systematic review, meta-analysis and bioinformatics study Lin Wang Abstract Background: The …

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