[1214] Expression of CD137 Protein in Select Hematopoietic Tumors: Implications for Anti-CD137 Immunomodulatory Therapy.

Matthew W Anderson, Aharon G Freud, Shuchun Zhao, Arash A Alizadeh, Holbrook E Kohrt, Roger Warnke, Ronald Levy, Yasodha Natkunam. Stanford, Stanford, CA

Background: CD137 (4-1BB), a tumor necrosis factor family member, is a co-stimulatory molecule expressed on a variety of hematopoietic cells, including T, NK and follicular dendritic cells (FDC). We previously constructed a two-gene model showing that the expression of CD137 and the germinal center (GC) marker LMO2, powerfully predicts outcome in patients with diffuse large B-cell lymphoma. Anti-CD137 agonistic antibodies have shown therapeutic efficacy in human solid-organ malignancies and mouse models of lymphoma and myeloma. We characterized the expression pattern of the CD137 protein to better understand its role in normal immune response and lymphomagenesis.
Design: An anti-CD137 antibody (clone BBK-2, Thermo Scientific, Fremont, CA) was optimized for use on paraffin tissue and then used to characterize CD137 protein expression in hematolymphoid tissues by immunofluorescence, immunohistochemistry and tissue microarrays.
Results: In normal hematopoietic tissues, CD137 protein is expressed by FDC in GC and scattered paracortical T cells, but not by normal GC B cells, bone marrow progenitor cells or maturing thymocytes. Most mature B cell lymphomas lack CD137 expression in tumor cells, although a significant proportion show variable numbers of CD137-positive infiltrating host cells. Classical Hodgkin lymphoma cells but not nodular lymphocyte predominant Hodgkin lymphoma cells, exhibit strong and consistent expression of CD137. CD137 is expressed by mature T-cell and extranodal NK/T cell lymphomas and FDC neoplasms, but is not observed in histiocytic tumors, myeloid or lymphoid leukemias or plasma cell neoplasms.

Expression of CD137 Protein in Hematopoietic Neoplasia
Tumor subtypeTotal positive
Mature B cell lymphomas0/435 (0%)
Mature T cell lymphomas16/21 (76%)
Extranodal NK/T cell lymphoma34/93 (35%)
Plasma cell neoplasms0/158 (0%)
Classical Hodgkin lymphoma179/208 (88%)
Lymphocyte predominant Hodgkin lymphoma0/17 (0%)
Histiocytic neoplasms0/20 (0%)
Follicular dendritic cell sarcoma6/7 (86%)
Acute leukemias0/25 (0%)

Conclusions: CD137 protein is a novel immunohistochemical marker for a select group of hematolymphoid tumors including classical Hodgkin lymphoma, T and NK cell lymphomas, and FDC neoplasms. CD137 protein is also expressed by normal immune cell subsets including FDC networks and infiltrating cells in the host response to lymphoma. These findings provide new insights for the use of anti-CD137 immunomodulatory therapy in lymphoid malignancies.
Category: Hematopathology

Monday, February 28, 2011 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 189, Monday Morning


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