Signaling Lymphocyte Activation Marker Family member 7 (SLAMF7) is highly expressed on human plasma cells and malignant myeloma cells, which is a therapeutic target for the anti-SLAMF7 antibody elotuzumab. Lower expression of SLAMF7 is found in NK cells, NK-like T cells, CD8+ T cells, activated monocytes and dendritic cells. With the exception of plasmablastic lymphoma and multiple myeloma, SLAMF7 was never been reported to be expressed in other malignant hematological diseases.
This prompted us to examine the expression of SLAMF7 also in T-cell lymphoma, NK/T-cell lymphoma, NK cell derived large granular lymphocyte (NK-LGL) and T-cell LGL.
We examined in biopsy tissue or blood samples of 11 patients with histologically proven NK/T-cell lymphomas, T-cell lymphoma, T-ALL, non-malignant Kikuchi necrotizing lymphadenitis, NK-LGL and T-LGL SLAMF7 expression by immunohistochemistry (IHC) or flow cytometry. We defined SLAMF7 as positive if we detected SLAMF7 expression in at least 20% of lymphoma cells by IHC or 10% by flow cytometer. As positive controls for SLAMF7 expression we used biopsy tissue from patients with multiple myeloma.
Here we found a strong expression of SLAMF7 by IHC in all 3 patients with NK/T-cell lymphoma, whereas no expression by IHC was found on T-cell lymphoma biopsy tissue of 3 patients with T-cell lymphoma and of 1 patient with T-ALL. Another patient who was suspected with T-cell lymphoma but later diagnosed as non-malignant Kikuchi necrotizing lymphadenitis, was tested weak positive for SLAMF7 expression by IHC as shown in table 1. Strong SLAMF7 expression was specific to lymphoma tissue in a patient with NK/T-cell lymphoma but not found in the surrounding healthy tissue of nasal epithelial cells as shown in figure 1, which identifies SLAMF7 as a suitable biomarker for NK/T-cell lymphoma. We detected SLAMF7 also in a patient with CD3-/CD56+/CD16+ NK-LGL cells and a further patient with CD3+/CD56+/CD8+ T-LGL by flow cytometer. Interestingly, 100% of NK-LGL cells (38,9% of all mononucleated cells in peripheral blood) and all T-LGL cells (17,2% of all mononucleated cells in peripheral blood) were SLAMF7 positive.
Here we report for the first time expression of SLAMF7 in NK/T-cell lymphoma and NK-LGL and T-LGL, which has clinical relevance because it extends possible immunotherapy to SLAMF7 inhibitor elotuzumab. SLAMF7 might also be a suitable target for CAR-T cell therapies as already used successfully in multiple myeloma trials. Nevertheless, it might be useful as a biomarker for NK/T-cell lymphomas and LGL, too.