CD30 characterizes polylobated lymphocytes and disease progression in HTLV-1-infected individuals

Purpose: Although expression of CD30 is reported in a subset of adult T-cell leukemia/lymphoma (ATL) cases, its clinicopathological significance is poorly understood. We aimed to characterize CD30-positive cells, and clarify their tumorigenic role in human T-cell lymphotropic virus type 1 (HTLV-1)-infected cells. Experimental Design: CD30-positive peripheral blood mononuclear cells from individuals with differing HTLV-1 disease status were characterized, and the role of CD30 signaling was examined using HTLV-1-infected cell lines and primary cells. Results: CD30-positive cells were detected in all samples examined, and the marker was co-expressed with both CD25 and CD4. This cell population expanded in accordance with disease progression. CD30-positive cells showed polylobation, with some possessing "flower cell" features, active cycling and hyperploidy. CD30 stimulation of HTLV-1 infected cell lines induced these features and abnormal cell division, with polylobation found to be dependent on the activation of phosphoinositide 3-kinase (PI3K). The results thus link the expression of CD30, which serves as a marker for HTLV-1 disease status, to an active proliferating cell fraction featuring polylobation and chromosomal aberrations. In addition, brentuximab vedotin, an anti-CD30 monoclonal antibody conjugated with auristatin E, was found to reduce the CD30-positive cell fraction. Conclusions: Our results indicate that CD30-positive cells act as a reservoir for tumorigenic transformation and clonal expansion during HTLV-1 infection. The CD30-positive fraction may thus be a potential molecular target for those with differing HTLV-1 disease status.

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