CD20-bearing extracellular vesicles are associated with prognostic biomarkers of patients with AIDS-NHL.

CD20 is a tetraspan membrane-bound protein vital for the development, activation, and differentiation of human B-cells. Non-Hodgkin lymphoma (NHL) is the most common hematological cancer in people living with (PLWH), and most B-cell NHLs express CD20. Extracellular vesicles (EVs) are nanosized vesicles released by cells into the extracellular environment. Here, we examined the association between plasma-derived CD20(+) EVs and prognostic biomarkers in the AIDS Malignancy Consortium (AMC) 034 trial. We isolated EVs from plasma of patients with AIDS-NHL before and after initiation of treatment (rituximab plus concurrent infusional EPOCH), measuring CD20 on EVs by ELISA. Ramos cells were treated with EVs isolated from NHL and AIDS-NHL lymphoma cell lines in the presence of rituximab to measure if EVs protect cells from rituximab cytotoxicity. Baseline plasma levels of CD20(+) EVs were significantly higher in non-responders and in patients with diffuse large B-cell lymphoma (DLBCL) with high International Prognostic Index (IPI) scores (2 to 3) compared to those with lower IPI scores (0 to 1). Moreover, baseline plasma levels of CD20(+) EVs were significantly associated with baseline levels of prognostic biomarkers for AIDS-NHL. We further demonstrate that EVs from NHL and AIDS-NHL cell lines can sequester rituximab and inhibit apoptosis.