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Expression of PD-1 (CD279) in cutaneous B-cell lymphomas with correlation to lymphoma entities and biologic behaviour


Mitteldorf, C; Bieri, M; Wey, N; Kerl, K; Kamarachev, J; Pfaltz, M; Kutzner, H; Roncador, G; Tomasini, D; Kempf, W (2013). Expression of PD-1 (CD279) in cutaneous B-cell lymphomas with correlation to lymphoma entities and biologic behaviour. British Journal of Dermatology, 169(6):1212-1218.

Abstract

BACKGROUND: Programmed death-1 (PD-1/CD279) is a cell surface protein expressed in activated T-cells and in a subset of T lymphocytes including follicular helper T-cells (TFH ). The interaction between PD-1 and its ligands plays a role in immune response, but also in immune evasion of malignancies. In nodal follicular lymphoma, the number of intratumoral PD-1 positive lymphocytes is associated with overall survival.
OBJECTIVES: We investigated 28 cases of PCBCL including primary cutaneous follicle center lymphoma (PCFCL; n=10), primary cutaneous marginal zone lymphoma (PCMZL; n=10) and diffuse large B-cell lymphoma, leg type (DLBCL-LT; n=8) for the number and density of PD-1 positive cells.
METHODS: Immunohistochemical stainings were performed. We used a computerized morphometric analysis for evaluation. The results were correlated with the clinical outcome. To distinguish between activated T-cells and TFH we performed PD-1/bcl-6 double staining and compared these results with CXCL-13. A double staining for PD-1 and PAX-5 was added to investigate if the tumor cells were positive for PD-1.
RESULTS: The PD-1 positive cells represented tumor infiltrating T-cells (TIL). Only a little subset (on average 12%) was represented by TFH . Patients with DLBCL-LT had a significant lower number of PD-1 positive TILs than PCMZL (p = 0.012) and PCFCL (p = 0.002) or both groups together (p = 0.001). The difference between PCMZL and PCFCL did not reach significance (p = 0.074). The tumor-cells were negative for PD-1.
CONCLUSIONS: A higher number of PD-1 expressing cells was found in indolent PCMZL and PCFCL in contrast to DLBCL-LT. The PD-1 positive cells in our study do not only represent TFH , but also by other activated T-cells as a part of the tumor microenvironment. The tumor cells in all investigated types of PCBCL did not show aberrant PD-1 expression. This article is protected by copyright. All rights reserved.

Abstract

BACKGROUND: Programmed death-1 (PD-1/CD279) is a cell surface protein expressed in activated T-cells and in a subset of T lymphocytes including follicular helper T-cells (TFH ). The interaction between PD-1 and its ligands plays a role in immune response, but also in immune evasion of malignancies. In nodal follicular lymphoma, the number of intratumoral PD-1 positive lymphocytes is associated with overall survival.
OBJECTIVES: We investigated 28 cases of PCBCL including primary cutaneous follicle center lymphoma (PCFCL; n=10), primary cutaneous marginal zone lymphoma (PCMZL; n=10) and diffuse large B-cell lymphoma, leg type (DLBCL-LT; n=8) for the number and density of PD-1 positive cells.
METHODS: Immunohistochemical stainings were performed. We used a computerized morphometric analysis for evaluation. The results were correlated with the clinical outcome. To distinguish between activated T-cells and TFH we performed PD-1/bcl-6 double staining and compared these results with CXCL-13. A double staining for PD-1 and PAX-5 was added to investigate if the tumor cells were positive for PD-1.
RESULTS: The PD-1 positive cells represented tumor infiltrating T-cells (TIL). Only a little subset (on average 12%) was represented by TFH . Patients with DLBCL-LT had a significant lower number of PD-1 positive TILs than PCMZL (p = 0.012) and PCFCL (p = 0.002) or both groups together (p = 0.001). The difference between PCMZL and PCFCL did not reach significance (p = 0.074). The tumor-cells were negative for PD-1.
CONCLUSIONS: A higher number of PD-1 expressing cells was found in indolent PCMZL and PCFCL in contrast to DLBCL-LT. The PD-1 positive cells in our study do not only represent TFH , but also by other activated T-cells as a part of the tumor microenvironment. The tumor cells in all investigated types of PCBCL did not show aberrant PD-1 expression. This article is protected by copyright. All rights reserved.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Psychiatry and Psychotherapy
04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:16 Aug 2013 07:22
Last Modified:05 Apr 2016 16:54
Publisher:Wiley-Blackwell
ISSN:0007-0963
Publisher DOI:https://doi.org/10.1111/bjd.12579
PubMed ID:23937075

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