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High proportions of...
High proportions of PD-1+ and PD-L1+ leukocytes in classical Hodgkin lymphoma microenvironment are associated with inferior outcome
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- Hollander, Peter (author)
- Uppsala universitet,Klinisk och experimentell patologi,Rose-Marie Amini
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- Kamper, Peter (author)
- Aarhus Univ Hosp, Dept Hematol, Aarhus, Denmark.
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- Smedby, Karin Ekstrom (author)
- Karolinska Institutet
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- Enblad, Gunilla (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Ludvigsen, Maja (author)
- Aarhus Univ Hosp, Dept Hematol, Aarhus, Denmark.
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- Mortensen, Julie (author)
- Aarhus Univ Hosp, Dept Hematol, Aarhus, Denmark.
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- Amini, Rose-Marie (author)
- Uppsala universitet,Klinisk och experimentell patologi,Rose-Marie Amini
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- Hamilton-Dutoit, Stephen (author)
- Aarhus Univ Hosp, Inst Pathol, Aarhus, Denmark.
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- d'Amore, Francesco (author)
- Aarhus Univ Hosp, Dept Hematol, Aarhus, Denmark.
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- Molin, Daniel, 1969- (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Glimelius, Ingrid, 1975- (author)
- Karolinska Institutet,Uppsala universitet,Experimentell och klinisk onkologi,Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.
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(creator_code:org_t)
- 2017-08-08
- 2017
- English.
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 1:18, s. 1427-1439
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Abstract
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- Immune checkpoint inhibition targeting the programmed death receptor (PD)-1 pathway is a novel treatment approach in relapsed and refractory classical Hodgkin lymphoma (cHL). Identifying patients with a high risk of treatment failure could support the use of PD-1 inhibitors as front-line treatment. Our aim was to investigate the prognostic impact of PD-1, programmed death-ligand 1 (PD-L1), and PD-L2 in the tumor microenvironment in diagnostic biopsies of patients with cHL. Patients from Denmark and Sweden, diagnosed between 1990 and 2007 and ages 15 to 86 years, were included. Tissue microarray samples were available from 387 patients. Immunohistochemistry was used to detect PD-1, PD-L1, and PD-L2, and the proportions of positive cells were calculated. Event-free survival (EFS; time to treatment failure) and overall survival (OS) were analyzed using Cox proportional hazards regression. High proportions of both PD-1(+) (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.10-2.86) and PD-L1(+) (HR 5 1.89; 95% CI, 1.08-3.30) leukocytes in the microenvironment were associated with inferior EFS in a multivariate analysis (adjusted for white blood cell count >15 x 10(9)/L, hemoglobin <105 g/L, albumin <40 g/L, B symptoms, extranodal involvement, stage, bulky tumor, nodular sclerosis subtype, Epstein-Barr virus status, lymphocyte count <0.6 x 10(9)/L, sex, and country). A high proportion of PD-L1(+) leukocytes was also associated with inferior OS in a multivariate analysis (HR, 3.46; 95% CI, 1.15-10.37). This is the first study to show a correlation after multivariate analysis between inferior outcome in cHL and a high proportion of both PD-1(+) and PD-L1(+) leukocytes in the tumor microenvironment.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Keyword
- Pathology
- Patologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Hollander, Peter
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Kamper, Peter
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Smedby, Karin Ek ...
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Enblad, Gunilla
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Ludvigsen, Maja
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Mortensen, Julie
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Amini, Rose-Mari ...
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Hamilton-Dutoit, ...
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d'Amore, Frances ...
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Molin, Daniel, 1 ...
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Glimelius, Ingri ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Clinical Laborat ...
- Articles in the publication
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Blood Advances
- By the university
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Uppsala University
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Karolinska Institutet