Expression of B7-H3 (CD276) an Immunoregulatory Cell Surface Molecule in Non-Hodgkin Lymphomas Identified by Mass Spectrometry.
Elizabeth A Wey, Julie Laliberta, Carla McNeil, Venkatesha Basrur, Farah Keyoumarsi, Dafydd Thomas, Cheolwon Suh, Jooryung Huh, Kojo Elenitoba-Johnson, Megan S Lim. University of Michigan, Ann Arbor; Asan Medical Center, Seoul, Korea
Background: B7-H3 is a member of the B7/CD28 superfamily of immunoregulatory molecules. Inhibition of T-cell mediated antitumor immunity by B7-H3 is involved in the immune evasion activity of cancer. Its expression is associated with increased risk of recurrence and poor survival in prostate and renal cancers. Using mass spectrometry-based glycoproteomic profiling, we identified B7-H3 as a selectively expressed protein in anaplastic large cell lymphoma (ALCL)-derived cell lines. We hypothesized that B7-H3 is expressed in distinct categories of human lymphoma.
Design: Lymphoma derived cell lines from B and T-cell lineage (n=10) were used for western blot analyses. Immunohistochemistry was performed on lymphoma tissue microarrays composed of 828 lymphomas using anti-human B7-H3 antibody and were evaluated using a combination of staining intensity and percentage of immunoreactive neoplastic cells.
Results: Western blot analysis demonstrated selective expression of B7-H3 in 3/5 ALCL-derived cell lines. B-cell lymphoma-derived cell lines did not express B7-H3. In reactive lymph nodes, B7-H3 was primarily expressed in the germinal center B-cells and in the follicular dendritic cells. B7-H3 was expressed in neoplastic cells of 6/32 (18.8%) ALCL, independent of ALK status and in 11/92 (12%) of other PTCL. Only rare cases (21/704) of other lymphoma subtypes expressed B7-H3.
|Follicular Lymphoma||1.1% (2/183)|
|Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma||1.2% (1/82)|
|Mantle Cell Lymphoma||0% (0/26)|
|Diffuse Large Cell Lymphoma||4.1% (10/245)|
|Hodgkin Lymphoma||5.3% (8/150)|
|Nodular Lymphocyte Predominant Hodgkin Lymphoma||0% (0/18)|
|Anaplastic Large Cell Lymphoma||18.8% (6/32)|
|Peripheral T Cell Lymphoma||12% (11/92)|