ABSTRACT
OBJECTIVES: To evaluate the expression of CD335 (NKp46), an activation receptor that is selectively expressed on natural killer (NK) cells. METHODS: We assessed CD335's potential utility as a diagnostic marker in 657 cases by flow cytometry and 410 cases by immunohistochemistry. RESULTS: We observed that CD335 was highly specific for NK cells in nonneoplastic tissues. Moreover, 61 (90%) of 68 of NK cell neoplasms demonstrated CD335 expression, whereas B-cell, myelomonocytic, and plasma cell neoplasms lacked expression. Notably, 16 (20%) of 82 mature T-cell neoplasms, particularly T-cell large granular lymphocytic leukemia, mycosis fungoides, and ALK+ anaplastic large cell lymphoma, aberrantly expressed CD335. CONCLUSIONS: Collectively, these data support the diagnostic utility of CD335 in evaluating hematopoietic malignancies and suggest that CD335 could be a useful target for selective immunotherapy in patients with mature NK and T-cell neoplasms.
Subject(s)
Biomarkers, Tumor/analysis , Hematologic Neoplasms/diagnosis , Killer Cells, Natural/immunology , Natural Cytotoxicity Triggering Receptor 1/biosynthesis , T-Lymphocytes/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Flow Cytometry , Hematologic Neoplasms/immunology , Hematologic Neoplasms/metabolism , Humans , Immunohistochemistry , Infant , Killer Cells, Natural/metabolism , Killer Cells, Natural/pathology , Male , Middle Aged , Natural Cytotoxicity Triggering Receptor 1/analysis , T-Lymphocytes/metabolism , T-Lymphocytes/pathologyABSTRACT
CD137 (also known as 4-1BB and TNFRSF9) is a member of the tumor necrosis factor receptor superfamily. Originally identified as a costimulatory molecule expressed by activated T cells and NK cells, CD137 is also expressed by follicular dendritic cells, monocytes, mast cells, granulocytes, and endothelial cells. Anti-CD137 immunotherapy has recently shown promise as a treatment for solid tumors and lymphoid malignancies in preclinical models. We defined the expression of CD137 protein in both normal and neoplastic hematolymphoid tissue. CD137 protein is expressed by follicular dendritic cells in the germinal center and scattered paracortical T cells, but not by normal germinal-center B cells, bone marrow progenitor cells, or maturing thymocytes. CD137 protein is expressed by a select group of hematolymphoid tumors, including classical Hodgkin lymphoma, T-cell and NK/T-cell lymphomas, and follicular dendritic cells neoplasms. CD137 is a novel diagnostic marker of these tumors and suggests a possible target for tumor-directed antibody therapy.
