CD137 Ligand Is Expressed in Primary and Secondary Lymphoid Follicles and in Select B-Cell Lymphomas: Diagnostic and Therapeutic Implications
Shuchun Zhao, Haiyu Zhang, Ying Xing, Yasodha Natkunam. Stanford University School of Medicine, Stanford, CA; Zhengzhou University School of Medicine, Zhengzhou, Henan, China
Background: CD137 ligand (4-1BB ligand, TNFSF9, CD137L), a member of the tumor-necrosis factor family, is a co-stimulatory molecule expressed mainly on activated antigen presenting cells including B cells, macrophages, and monocytes. Its cognate receptor CD137 has emerged as an important target for anti-cancer therapies through immunomodulation in hematopoietic neoplasms. We previously reported the tissue distribution profile of CD137; here we undertook an extensive characterization of CD137L in a large collection of well annotated human hematopoietic samples in order to better understand its role in the normal immune response and lymphomagenesis.
Design: A rabbit polyclonal anti-CD137L (Abcam, Cambridge, MA) was optimized for use on paraffin-embedded tissue to characterize CD137L protein expression in both normal and neoplastic hematolymphoid tissue utilizing immunofluorescence, immunohistochemistry, and tissue microarrays.
Additional flow cytometry was performed using monoclonal CD137L PE (BD Biosciences, CA).
Results: CD137L is preferentially expressed in B cells of the primary follicles, mantle zones of secondary follicles and weakly in germinal centers. Double labeling further showed that CD137L is a potential new marker of memory B cells. The majority of B cell lymphomas expressed CD137L including diffuse large B cell (83), follicular (131), and mantle cell (29) lymphomas. Hodgkin and T cell lymphomas lacked CD137L expression in tumor cells, although variable numbers of CD137L-positive infiltrating host cells were present (Table 1).
Conclusions: CD137L protein is a novel marker for a select group of hematolymphoid tumors including diffuse large B cell, follicular and mantle cell lymphomas. In addition, our observations suggest that CD137L is a potential new memory B cell marker. These findings suggest that CD137L is likely to be a valuable target for immunotherapy for patients harboring these hematopoietic tumors.
|Diffuse Large B cell cell||65/83||78|
|Peripheral T cell||0/31||0|
|Plasma Cell Myeloma||9/132||7|
|Lymphocyte Predominant Hodgkin||0/33||0|