Detection of Aberrant CD58 Expression in a Wide Spectrum of Lymphoma Subtypes: Implications for Treatment Resistance.

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Abstract

CD58 or lymphocyte function-associated antigen-3, is a ligand for CD2 receptors on T- and NK-cells and is required for their activation and target cell killing. We recently showed a trend towards higher frequency of CD58 aberrations in patients with diffuse large B-cell lymphoma (DLBCL) who progressed on CAR-T cell treatment compared to those who responded. Given that CD58 status may be an important measure of T-cell mediated therapy failure, we developed CD58 immunohistochemical assay and evaluated CD58 status in 748 lymphomas. Our results show that CD58 protein expression is downregulated in a significant proportion of all subtypes of B- T- and NK-cell lymphomas. CD58 loss is significantly related to poor prognostic indicators in DLBCL and to ALK and DUSP22 rearrangements in anaplastic large cell lymphoma. However, it is not associated with overall or progression free survival in any of the lymphoma subtypes. As eligibility for CAR-T therapy is being extended to a broader spectrum of lymphomas, mechanisms of resistance, such as target downregulation and CD58 loss, may limit therapeutic success. CD58 status is therefore an important biomarker in lymphoma patients who may benefit from next generation T-cell mediated therapies or other novel approaches that mitigate immune escape.

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