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Tumor Microenvironm...
Tumor Microenvironment and Checkpoint Molecules in Primary Cutaneous Diffuse Large B-Cell Lymphoma - New Therapeutic Targets
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Mitteldorf, C. (författare)
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Berisha, A. (författare)
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Pfaltz, Monique C. (författare)
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Broekaert, S. M. C. (författare)
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Schän, M. P. (författare)
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Kerl, K. (författare)
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Kempf, W. (författare)
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- Lippincott Williams and Wilkins, 2017
- 2017
- Engelska.
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Ingår i: American Journal of Surgical Pathology. - : Lippincott Williams and Wilkins. - 0147-5185 .- 1532-0979. ; 41:7, s. 998-1004
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Programmed death ligand 1 (PD-L1) is expressed by 20% to 57% of systemic diffuse large B cell lymphomas (DLBCLs). PD-L1 expression in primary cutaneous DLBCL (pcDLBCL) has not been studied so far. Sixteen paraffin-embedded tissue samples of pcDLBCL (13 leg type [LT], 3 others [OT]) were investigated for PD-1, PD-L1, and CD33 expression and the cellular composition of the tumor microenvironment, focusing on myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages. Membrane-bound PD-L1 expression by the tumor cells was observed in all samples, albeit to a variable extent (19.9%). As expected, most DLBCL-LT (10 cases) were classified as activated B cell like type, with a higher PD-L1 score (21.9%) compared with that of the germinal center B cell like type (7.7%). The surrounding infiltrate consisted predominately of CD163(+) M2 rather than CD68(+) macrophages (CD68:CD163=1:4 to 6). Moreover, a considerable proportion of CD33(+) MDSCs with PD-L1 coexpression was admixed. Tumor cells expressed CD33 to variable degrees (2% to 60%). The number of MDSCs or M2 macrophages did not correlate with pcDLBCL subtypes LT or OT. T cells were only a minor component of the tumor microenvironment. We propose that PD-L1(+) tumor cells and PD-L1(+) MDSCs shield the tumor against PD-1(+) tumor-infiltrating lymphocytes, consequently leading to inhibition and diminution of tumor-infiltrating lymphocytes. Moreover, we found a polarization to M2 macrophages, which may contribute to the poor prognosis of DLBCL patients. Thus, targeting of tumor cells and MDSCs using anti-PD-1/anti-PD-L1 or anti-CD33 antibodies might be a worthwhile new approach to treat this aggressive form of cutaneous B-cell lymphoma. © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- CD274 protein
- human
- CD33 antigen
- CD33 protein
- human
- PDCD1 protein
- human
- programmed death 1 ligand 1
- programmed death 1 receptor
- tumor marker
- adult
- aged
- case control study
- diffuse large B cell lymphoma
- female
- human
- male
- metabolism
- middle aged
- pathology
- retrospective study
- skin tumor
- tumor microenvironment
- very elderly
- Adult
- Aged
- Aged
- 80 and over
- Antigens
- CD274
- Biomarkers
- Tumor
- Case-Control Studies
- Female
- Humans
- Lymphoma
- Large B-Cell
- Diffuse
- Male
- Middle Aged
- Programmed Cell Death 1 Receptor
- Retrospective Studies
- Sialic Acid Binding Ig-like Lectin 3
- Skin Neoplasms
- Tumor Microenvironment
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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