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

## TL;DR

This study shows that CD20-positive extracellular vesicles in the blood of AIDS-related lymphoma patients are linked to poor prognosis and may protect cancer cells from treatment.

## Contribution

The study identifies CD20+ EVs as a novel biomarker and potential mechanism of resistance to rituximab in AIDS-related NHL.

## Key findings

- Baseline CD20+ EV levels were higher in non-responders and patients with high IPI scores.
- CD20+ EVs were associated with prognostic biomarkers in AIDS-NHL patients.
- EVs from NHL cell lines can bind rituximab and reduce cell death.

## Abstract

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.

The online version contains supplementary material available at 10.1038/s41598-025-11128-1.