programmed death ligand 1 pd l1

 Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via, Yoshimura Statistical analysis: Inoue, Inui, Karayama, Yasui. Evaluation of Programmed Death Ligand 1 (PD-L1) Gene Amplification and Response to Nivolumab Monotherapy in Non–small Cell Lung Cancer. Â, Miao  MD, Snyder  et al.  M, Lefebvre 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. We thank the Edanz Group for editing a draft of this article.  Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. , Le Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. This study reveals the molecular details of the human PD-1/PD-L1 interaction based on an X-ray structure of the complex.  A, Response was assessed every 4 cycles (ie, 8 weeks) using RECIST version 1.1 by local investigators. The structural rearrangement within the CC′ loop upon complex formation is clearly discernible. 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 … Supervision: Inui, Karayama, Hozumi, Suzuki, Enomoto, Sugimura, Suda. 2020 Nov 20;23(12):101835. doi: 10.1016/j.isci.2020.101835.  RH, Ligon Guzik K, Zak KM, Grudnik P, Magiera K, Musielak B, Törner R, Skalniak L, Dömling A, Dubin G, Holak TA.  MR, Monti HHS T cell activation by immune allorecognition is a major contributing factor toward the triggering of organ rejection. BMC Bioinformatics. 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.  AM, Piccioni PD-L1 and CEP9 signals are shown in red and green, respectively. 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. 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).  A transcriptionally and functionally distinct PD-1, Lu The findings of this study suggest that PD-L1 amplification in non–small cell lung cancer is associated with durable benefit from nivolumab treatment. The interaction between PD …  T, Rizvi Understanding the Targeting Mechanisms of Multi-Specific Biologics in Immunotherapy with Multiscale Modeling.  CF, Proverbs-Singh  R. Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1). JAMA Network Open. 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. Customize your JAMA Network experience by selecting one or more topics from the list below. COVID-19 is an emerging, rapidly evolving situation. This patient received 21 cycles of nivolumab with a PFS of 9.7 months (eTable in the Supplement).  et al. In contrast, the 1-year PFS and 1-year OS rates were only 18.5% (95% CI, 6.7%-34.8%) and 46.0% (95% CI, 26.4%-63.6%) for patients with PD-L1 polysomy and 20.8% (95% CI, 14.8%-27.4%) and 57.6% (95% CI, 49.6%-64.8%) for patients with PD-L1 disomy, respectively. 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. Close-Up Views of the hPD-1/hPD-L1 Interface, hPD-1 and hPD-L1 are represented by blue…, Figure 3. Programmed death-ligand 1, commonly abbreviated PD-L1, is a protein with an important role in immune system regulation and cancer.  et al. Computed Tomography Scans Before and After Treatment With Nivolumab in a Patient with PD-L1–Amplified Adenocarcinoma, eFigure 5.  et al; KEYNOTE-024 Investigators. © 2020 Inoue Y et al.  Genomic features of response to combination immunotherapy in patients with advanced non–small cell lung cancer. , Rizvi  H, Nivolumab was discontinued in 178 patients (91.8%), mainly due to disease progression (135 [69.6%]) and adverse events (37 [19.1%]).  S, An OS benefit for patients with high expression of PD-L1 compared with those with low expression of PD-L1 was observed at the PD-L1 TPS threshold of 50% (HR, 0.44; 95% CI, 0.23-0.84; P = .01) (eFigure 8A in the Supplement), but again, no significant benefit was observed at lower PD-L1 TPS thresholds (eFigures 8B, 8C, and 8D in the Supplement). By continuing to use our site, or clicking "Continue," you are agreeing to our, 2020 American Medical Association. All Rights Reserved. Structure.  et al.  Heterogeneity analysis of PD-L1 expression and copy number status in EBUS-TBNA biopsy specimens of non–small cell lung cancer: comparative assessment of primary and metastatic sites. , Ready Choi JG, Kim YS, Kim JH, Kim TI, Li W, Oh TW, Jeon CH, Kim SJ, Chung HS.  VH, Herzig グナルの亢進／抑制に働く CD28/CTLA-4 ファミリーに属する、50～55 kDa のI型膜たんぱく質です。.  JN, Smith  PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. , Barrett  Nivolumab versus docetaxel in advanced nonsquamous non–small cell lung cancer. .  MT, Anderson 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. Funding/Support: This was an investigator-initiated study supported by Ono Pharma and Bristol-Myers Squibb. (A and B) Surface representation of the hPD-L1 binding site of hPD-1. hPD-1 and hPD-L1 are represented by blue and green ribbons, respectively. Clipboard, Search History, and several other advanced features are temporarily unavailable.  Clinical significance of PD-L1 and PD-L2 copy number gains in non–small cell lung cancer. , Ikeda  Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors. , Ansell The Fisher exact test was used for categorical variables. In addition, PD-L1 amplification was shown to enhance PD-L1 induction in response to cytokines, such as interferon-γ and tumor necrosis factor α, as adaptive immune resistance in preclinical models of lung and breast cancer.23,24 Moreover, tumor PD-L1 amplification was associated with a specific type of TME, defined by high PD-L1 and CD8A (OMIM 186910) expression.25 This TME characterized by PD-L1–positive tumors and enriched cytotoxic immune cells appears to be associated with response to PD-1/PD-L1 inhibitors. Herbst 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. OS was defined as the interval from the date of the first administration of nivolumab to the date of death from any cause.  DT, Uram  DG, Egger Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, play an important role in the maintenance of peripheral tolerance. They were not compensated for their time. 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.  et al.  DT, Durham  Mutational landscape and sensitivity to immune checkpoint blockers. , Goodman (B) Back-side view. In this study, tumor PD-L1 amplification but not polysomy was associated with response to nivolumab monotherapy among patients with NSCLC.  M, 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. 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).  et al; OAK Study Group.  A, Barlesi  AM, Borrello Drafting of the manuscript: Inoue, Yoshimura, Inui, Karayama, Yasui, Hozumi, Suzuki, Furuhashi, Hashimoto, Inami, Sugimura, Suda.  et al. USA.gov. 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. The associations of tumor PD-L1 protein expression with PD-L1 copy number and outcomes were also included in the secondary end points. 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.  et al. Main Outcomes and Measures  Pretreatment tumor samples were collected for biomarker evaluation.  B, Andreozzi  P, Kim  et al. 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. All Rights Reserved, Challenges in Clinical Electrocardiography, Clinical Implications of Basic Neuroscience, Health Care Economics, Insurance, Payment, Scientific Discovery and the Future of Medicine, United States Preventive Services Task Force, 2020;3(9):e2011818. 2020 Oct 1;9(1):1818437. doi: 10.1080/2162402X.2020.1818437. B, Scatterplot depicting PD-L1 tumor proportion score and PD-L1 to CEP9 ratio (Spearman ρ = 0.12; 95% CI, −0.025 to 0.26; P = .10). 2017 Aug 1;25(8):1163-1174. doi: 10.1016/j.str.2017.06.011.  SJ, Villegas 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.  M, Cancer Treat Rev. Question   PD-L1 Is upregulated by simultaneous amplification of the, Chen Our website uses cookies to enhance your experience. (A) Apo-hPD-1. © 2020 American Medical Association. Front Immunol.  E, 2017 Jul 13;60(13):5857-5867. doi: 10.1021/acs.jmedchem.7b00293.  N, Besse 2017 May 2;13(5):892-900. doi: 10.1039/c7mb00036g.  JP; STROBE Initiative.  S, Stein 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. Biomarker evaluation samples were obtained mainly from primary lesions through several procedures, and the median (IQR) interval between the date of sample collection and nivolumab therapy initiation was 10.7 (5.8-16.8) months, with 111 samples (57.2%) collected within 12 months before treatment.  et al. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.27.  et al.  ME, Greenawalt C, Violin plot depicting PD-L1 tumor proportion score in association with PD-L1 copy number status.  J, Reckamp  MA. Administrative, technical, or material support: Inoue, Yoshimura, Nishimoto, Inui, Karayama, Furuhashi, Fujisawa, Asada, Uto, Matsui, Hashimoto, Toyoshima, Kusagaya, Sugimura.  DM,  Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. , Prelaj  Genomic correlates of response to immune checkpoint blockade. , Green Cox univariable proportional hazards regression model was used to explore the prognostic value of covariables. eCollection 2020. 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.  et al. 2017 Mar;54:99-109. doi: 10.1016/j.ctrv.2017.01.009. Median (interquartile range) duration of follow-up was 12.6 (5.6-20.4) months. No patients received ICIs before nivolumab. 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. 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. 2020 Dec 14;21(Suppl 17):557. doi: 10.1186/s12859-020-03904-9. 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 …  et al. Descriptive Statistics for PD-L1 FISH, eFigure 2. 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).  Nivolumab versus docetaxel in advanced squamous-cell non–small cell lung cancer. , Borghaei J Med Chem. Validation Study of the E1L3N Anti–PD-L1 Antibody, eFigure 4. Overall response rate (ORR) according to the PD-L1 copy number status.  S.  et al; PACIFIC Investigators. Accessibility Statement, Figure 1. doi:10.1001/jamanetworkopen.2020.11818. Patients with PD-L1 amplification showed excellent survival outcomes for progression-free and overall survival.  R, Ferrara  Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non–small cell lung cancer profiled with targeted next-generation sequencing. , Hellmann The median (IQR) follow-up period among 67 patients who were censored was 20.5 (15.4-30.4) months.  Predictive biomarkers of response for immune checkpoint inhibitors in non-small-cell lung cancer. , Le Response to Nivolumab According to PD-L1 Protein Expression, eFigure 7. Privacy Policy| Waterfall Plot Showing the Best Percentage Change From Baseline, eFigure 6. 2020 Nov 5;11:598556. doi: 10.3389/fimmu.2020.598556.  Y, Yoshimura  TA, Postow In terms of survival outcome, we observed only 1 event of progression (Figure 4A) and no deaths (Figure 4B) among patients with PD-L1 amplification, with a 1-year PFS rate of 80.0% (95% CI, 20.4%-96.9%) and 1-year OS rate of 100%. Targeting the programmed death-1 pathway in lymphoid neoplasms. iScience. 2016 May 24;7(21):30323-35. doi: 10.18632/oncotarget.8730. PD-L1 copy number was assessed by centrally performed FISH using the Histra PD-L1 FISH kit (Jokoh, Tokyo, Japan) as described elsewhere.22,28 This kit contains the spectrum orange-labeled bacterial artificial chromosome clone RP11-599H20 (9p24.1, PD-L1; Advanced GenoTechs) and the spectrum green-labeled control centromere enumeration probe for chromosome 9 (CEP9; RP11-113O24; Advanced GenoTechs) as PD-L1 locus–specific and referenced chromosome 9 FISH probes, respectively.  S, Rodig …  |   M, Pocock  et al.  Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer. , Inoue  S, Dercle All residues important for the interaction are highlighted as sticks. Not all submitted comments are published. Here, we showed dysregulation of programmed cell death-ligand 1/programmed cell death 1 (PD-L1/PD-1…  L, Ammari 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. 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. 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.  K, Inoue Conclusions and Relevance  Zak KM, Grudnik P, Guzik K, Zieba BJ, Musielak B, Dömling A, Dubin G, Holak TA.  KP, Van Allen Figure 1.  et al. 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. Response was assessed every 4 cycles using Response Evaluation Criteria in Solid Tumors version 1.1. Binding of hPD-L1 Induces Significant…, Figure 1. Programmed death-ligand 1 (PD-L1) protein. © 2020 American Medical Association.  D, Robinson  et al. By contrast, there were no significant differences in duration of PFS when stratified by lower PD-L1 TPS thresholds of 10% (eFigure 7B in the Supplement), 5% (eFigure 7C in the Supplement), and 1% (eFigure 7D in the Supplement). Partial Least-Squares Discriminant Analysis and Ensemble-Based Flexible Docking of PD-1/PD-L1 Inhibitors: A Pilot Study. This study reveals the molecular details of the human PD-1/PD-L1 interaction based on an X-ray structure of the complex. 4 Binding of PD-1 to its ligand PD-L1 expressed on …  EC, Elledge Sequential nivolumab was given on day 1 of a 14-day cycle. 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 … sign up for alerts, and more, to access your subscriptions, sign up for alerts, and more, to download free article PDFs, sign up for alerts, customize your interests, and more, to make a comment, download free article PDFs, sign up for alerts and more, Archives of Neurology & Psychiatry (1919-1959), Sign Up for Emails Based on Your Interests, FDA Approval and Regulation of Pharmaceuticals, 1983-2018, Global Burden of Skin Diseases, 1990-2017, Health Care Spending in the US and Other High-Income Countries, Life Expectancy and Mortality Rates in the United States, 1959-2017, Medical Marketing in the United States, 1997-2016, Practices to Foster Physician Presence and Connection With Patients in the Clinical Encounter, US Burden of Cardiovascular Disease, 1990-2016, US Burden of Neurological Disease, 1990-2017, Waste in the US Health Care System: Estimated Costs and Potential for Savings, Register for email alerts with links to free full-text articles. Third, we could not assess TMB and characteristics of the TME, mainly owing to the limited small biopsy samples. In this study, a selection of patients with NSCLC based on PD-L1 amplification was associated with greater durable benefit from nivolumab. Apo-hPD1 (PDB: 3RRQ) was overlaid on hPD-1 within the complex, and residues 62–82 of the former are shown (yellow ribbon). 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). ¥çš„に作った抗体で蓋をしてしまうことで結合を阻害しT細胞を抑制させない薬が認可され …  K, 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. Adverse events were graded based on the National Cancer Institute Common Toxicity Criteria version 4.0.  C, Marabelle PD-L1 CNGs were identified in 32 patients (16.5%), including 5 (2.6%) with amplification and 27 (13.9%) with polysomy. Acquisition, analysis, or interpretation of data: Inoue, Yoshimura, Nishimoto, Inui, Karayama, Yasui, Hozumi, Suzuki, Furuhashi, Fujisawa, Enomoto, Nakamura, Asada, Uto, Fujii, Matsui, Matsuura, Hashimoto, Toyoshima, Kusagaya, Matsuda, Inami, Kaida, Niwa, Ito, Sugimura.  S, Mol Biosyst.  CL, Yearley  A, Soria  I, The mechanisms by which PD-L1–amplified tumors are associated with long-lasting responses to nivolumab remain unclear.  PC, Vandenbroucke For PD-L1 IHC, 118 (60.8%) and 76 (39.2%) samples were assessed using the E1L3N and 22C3 antibodies, respectively.  et al. First, definite conclusions are still precluded because of the small number of patients with PD-L1 amplification. Within the complex structure, hPD-1 is colored blue and hPD-L1 is colored green; both are shown in stereo view in ribbon representation.  MG, Advani 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.  S, Three Main Hot Spots on the PD-L1 Surface, NLM Kuang Z, Heng Y, Huang S, Shi T, Chen L, Xu L, Mei H. ACS Omega. Please see our commenting policy for details.  EM. 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.  RS, Baas 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.  et al.  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. , von Elm PD-L1 TPS was only weakly correlated with PD-L1 copy number (ρ = 0.24; 95% CI, 0.10 to 0.37; P < .001) (Figure 2A) and was not correlated with the PD-L1 to CEP9 ratio (ρ = 0.12; 95% CI, −0.025 to 0.26; P = .10) (Figure 2B), despite a significant difference in PD-L1 expression levels according to the PD-L1 copy number status (Figure 2C).  MD, Awad 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. For the overall population, the ORR and disease control rate was 19.6% (95% CI, 14.2%-25.9%) and 50.5% (95% CI, 43.3%-57.8%), respectively.  Y. 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. Dr Suda reported receiving grants from Boehringer Ingelheim, AstraZeneca, Takeda Pharmaceutical Company, Kyorin Pharmaceutical Company, Shionogi and Co, Taiho Phamaceutical Co, Daiichi Sankyo Healthcare, and Pfizer outside the submitted work. Data were analyzed from December 2019 to February 2020. 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.  SM, Lesokhin Findings   Cancer immunology: mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. , Tumeh Gly124 Cleft ( L Tyr123-Accommodating…, Figure 3. The information will be posted with your response.  NA, Hellmann  T, Uno JAMA Netw Open. 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 …  D, Programmed cell death 1 ligand 1 (synonym CD274, B7 Homolog 1) ist ein Oberflächenprotein und beteiligt an der Hemmung der Immunantwort. 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. Exposures  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).

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