Peripheral CD8 effector-memory type 1 T-cells correlate with outcome in ipilimumab-treated stage IV melanoma patients
| العنوان: | Peripheral CD8 effector-memory type 1 T-cells correlate with outcome in ipilimumab-treated stage IV melanoma patients |
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| المؤلفون: | Christian U. Blank, Michele Maio, Michael A. Postow, Benjamin Weide, Phillip Wong, Dirk Schadendorf, Anna Maria Di Giacomo, Florian Heubach, Jianda Yuan, Paolo A. Ascierto, Amir Khammari, Marnix H Geukes Foppen, Brigitte Dréno, Graham Pawelec, Claus Garbe, Emanuela Romano, Domenico Mallardo, Bastian Schilling, Jedd D. Wolchok, Kilian Wistuba-Hamprecht, Alexander Martens |
| المساهمون: | Department of Dermatology [Tubingen, Germany], University Medical Center [Tubingen, Germany], Department of Internal Medicine II [Tübingen, Germany], University Medical Center [Tübingen, Germany], Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), The Netherlands Cancer Institute [Amsterdam, The Netherlands], Memorial Sloane Kettering Cancer Center [New York], Weill Medical College of Cornell University [New York], Istituto Nazionale Tumori Fondazione Pascale [Naples, Italy], Department of Dermatology [Essen, Germany], University Hospital [Essen, Germany]-West German Cancer Center [Essen, Germany]-University Duisburg-Essen [Germany], German Cancer Consortium [Heidelberg] (DKTK), Division of Medical Oncology and Immunotherapy [Siena, Italy], University Hospital of Siena, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), School of Science and Technology [Nottingham, U.K.], Nottingham Trent University, Division of Cancer Studies [London, UK], King‘s College London, Parts of this study were funded by Bristol-Myers Squibb (Munich, Germany) to B Weide. Parts of this study were funded by the EU Seventh Framework Program ‘PRIAT’ (Profiling Responders In Antibody Therapies) grant agreement no 305309 to C Garbe. Parts of this study were funded by Deutsche Forschungsgemeinschaft DFG PA 361-22/1 to G. Pawelec., European Project: 305309,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,PRIAT(2012), Bernardo, Elizabeth, Profiling Responders In Antibody Therapies - PRIAT - - EC:FP7:HEALTH2012-11-01 - 2014-10-31 - 305309 - VALID, Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Memorial Sloan Kettering Cancer Center [New York, NY, USA], Weill Cornell Medical College [New York, NY, USA], German Cancer Consortium - DKTK [Heidelberg, Germany], Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Nottingham Trent University [U.K.], European Project : 305309,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,PRIAT ( 2012 ), Universität Duisburg-Essen = University of Duisburg-Essen [Essen]-University Hospital [Essen, Germany]-West German Cancer Center [Essen, Germany] |
| المصدر: | European Journal of Cancer European Journal of Cancer, 2017, 73, pp.61-70. ⟨10.1016/j.ejca.2016.12.011⟩ European Journal of Cancer, Elsevier, 2017, 73, pp.61-70. 〈10.1016/j.ejca.2016.12.011〉 European Journal of Cancer, Elsevier, 2017, 73, pp.61-70. ⟨10.1016/j.ejca.2016.12.011⟩ |
| بيانات النشر: | Elsevier BV, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Oncology, Cancer Research, Skin Neoplasms, Programmed Cell Death 1 Receptor, Medizin, Kaplan-Meier Estimate, CD8-Positive T-Lymphocytes, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Biomarker, Effector memory cells, Ipilimumab, Melanoma, Prognosis, medicine.diagnostic_test, Effector, Antibodies, Monoclonal, Middle Aged, Flow Cytometry, Peripheral, 030220 oncology & carcinogenesis, Biomarker (medicine), Female, medicine.drug, Adult, medicine.medical_specialty, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Peripheral blood mononuclear cell, Article, Flow cytometry, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigens, Neoplasm, Internal medicine, Biomarkers, Tumor, medicine, Humans, Aged, business.industry, medicine.disease, 030104 developmental biology, Immunology, business, Immunologic Memory, CD8 |
| الوصف: | International audience; The role of the assessment of peripheral T-cell phenotypes in predicting overall survival (OS) after ipilimumab treatment is unclear. Here, we analysed mononuclear cells in the blood before and at different time points during treatment with ipilimumab in 137 late-stage melanoma patients. The proportions of baseline naïve and memory T-cells were measured by flow cytometry and correlated with OS, with an emphasis on PD-1 expression. High frequencies (>13%) of CD8 effector-memory type 1 (EM1) T-cells at baseline correlated with longer OS (p = 0.029) and higher clinical response rates (p = 0.01). The frequency of these EM1 cells and the M category had independent impacts on OS (hazard ratio = 1.5, p = 0.033; and hazard ratio = 1.9, p = 0.007). In contrast, high baseline frequencies of late stage-differentiated effector memory CD8 cells (>23.8%) were negatively associated with OS (p = 0.034) but did not correlate with clinical response. Following treatment, a decrease of CD8 cells from baseline to the time of the second drug dose and at later time points was strongly and consistently correlated with a high clinical response rate. Our observations thus suggest an important predictive role of baseline CD8 EM1 cells and changes in CD8 cells for clinical response of ipilimumab. Further validation of these biomarker candidates is warranted. |
| وصف الملف: | application/pdf |
| تدمد: | 0959-8049 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88a6982f18635313131b596d20ee2f8dTest https://doi.org/10.1016/j.ejca.2016.12.011Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....88a6982f18635313131b596d20ee2f8d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09598049 |
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