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.