Tumor Microenvironment and Checkpoint Molecules in Primary Cutaneous Diffuse Large B-Cell Lymphoma - New Therapeutic TargetsShow others and affiliations
2017 (English)In: American Journal of Surgical Pathology, ISSN 0147-5185, E-ISSN 1532-0979, Vol. 41, no 7, p. 998-1004Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
Lippincott Williams and Wilkins , 2017. Vol. 41, no 7, p. 998-1004
Keywords [en]
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
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:miun:diva-44512DOI: 10.1097/PAS.0000000000000851Scopus ID: 2-s2.0-85020736522OAI: oai:DiVA.org:miun-44512DiVA, id: diva2:1642026
2022-03-032022-03-032022-03-03Bibliographically approved