As checkpoint molecules’ inhibition may represent a therapeutic option in relapsing cases, we assessed programmed death ligands’ (PD-L1/PD-L2) expression in a series of 29 primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT) cases. Double immunostaining
for either PD-L1 or PD-L2 was associated either with PAX5 staining to evaluate tumor cells or with CD68 or CD163 staining for macrophages. The microenvironment of PCDLBCL-LT was characterized by immunostainings for CD3 (tumor-infiltrating lymphocytes), FOXP3 (regulatory T cells), programmed
cell death-1, and CD33 (myeloid-derived suppressor cells). The 9p24.1 locus encoding for PD-L1/PD-L2 was evaluated by fluorescence in situ hybridization. A PD-L1 expression was observed in all cases. However, double staining with PD-L1/PAX5 identified only 1 case harboring PD-L1 expression
by tumor cells. All cases displayed PD-L1 expression by numerous immune cells, characterized as CD68+ CD163+ M2 macrophages. A normal fluorescence in situ hybridization pattern was observed in 21 of 26 cases. Three cases (11.5%) harbored a low polysomy status including
the case with PD-L1 expression by tumor cells. Interestingly, 2 cases (7.7%) exhibited a PD-L1/PD-L2 locus break-apart pattern, and PD-L2 expression by tumor cells was observed. PD-L2 expression by tumor cells was not observed in the 24 cases without 9p24.1 rearrangement. Treating patients
with relapsing PCDLBCL-LT by using immune checkpoint inhibitors may have an indirect effect through immune cells, except in rare cases with 9p24.1 rearrangement leading to PD-L2 expression by tumor cells. Reprogramming tumor-associated macrophages with anticancer therapies is appealing in
such lymphoma subtypes wherein M2 macrophages represent the majority of immune cells.
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primary cutaneous diffuse large B-cell lymphoma leg type;
programmed death ligands
Document Type: Research Article
INSERM U1053, Team 3 Oncogenesis of Cutaneous Lymphomas, Pathology Department
INSERM U1053, Team 3 Oncogenesis of Cutaneous Lymphomas
INSERM U1053, Team 3 Oncogenesis of Cutaneous Lymphomas, Dermatology Department
INSERM U1053, Team 1 Liver Cancer and Tumor Invasion, University of Bordeaux
INSERM U1053, Team 3 Oncogenesis of Cutaneous Lymphomas, Tumor Biology and Tumor Bank Department, CHU Bordeaux, Bordeaux, France
Publication date: March 1, 2018