Plasma extracellular vesicles bearing PD-L1, CD40, CD40L or TNF-RII are significantly reduced after treatment of AIDS-NHL

Laura E Martínez; Shelly Lensing; Di Chang; Larry I Magpantay; Ronald Mitsuyasu; Richard F Ambinder; Joseph A Sparano; Otoniel Martínez-Maza; Marta Epeldegui

doi:10.1038/s41598-022-13101-8

Plasma extracellular vesicles bearing PD-L1, CD40, CD40L or TNF-RII are significantly reduced after treatment of AIDS-NHL

Sci Rep. 2022 Jun 2;12(1):9185. doi: 10.1038/s41598-022-13101-8.

Authors

Laura E Martínez^{1

2}, Shelly Lensing³, Di Chang³, Larry I Magpantay^{1

2}, Ronald Mitsuyasu¹, Richard F Ambinder⁴, Joseph A Sparano⁵, Otoniel Martínez-Maza^{1

2

6}, Marta Epeldegui^{7

8

9}

Affiliations

¹ UCLA AIDS Institute and David Geffen School of Medicine, University of California, Los Angeles, Biomedical Sciences Research Building Room 173, Los Angeles, CA, 90095, USA.
² Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
³ Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
⁴ Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, John Hopkins University, Baltimore, MD, USA.
⁵ Division of Hematology Oncology, Mount Sinai, NY, USA.
⁶ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA.
⁷ UCLA AIDS Institute and David Geffen School of Medicine, University of California, Los Angeles, Biomedical Sciences Research Building Room 173, Los Angeles, CA, 90095, USA. mepeldegui@mednet.ucla.edu.
⁸ Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. mepeldegui@mednet.ucla.edu.
⁹ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA. mepeldegui@mednet.ucla.edu.

Abstract

Emerging evidence shows that tumor cells secrete extracellular vesicles (EVs) that carry bioactive cell surface markers, such as programmed death-ligand 1 (PD-L1), which can modulate immune responses and inhibit anti-tumor responses, potentially playing a role in lymphomagenesis and in promoting the growth of these cancers. In this study, we investigated the role of EVs expressing cell surface molecules associated with B cell activation and immune regulation. We measured levels of EVs derived from plasma from 57 subjects with AIDS-related non-Hodgkin lymphoma (AIDS-NHL) enrolled in the AIDS Malignancies Consortium (AMC) 034 clinical trial at baseline and post-treatment with rituximab plus concurrent infusional EPOCH chemotherapy. We found that plasma levels of EVs expressing PD-L1, CD40, CD40L or TNF-RII were significantly reduced after cancer treatment. AIDS-NHL patients with the diffuse large B cell lymphoma (DLBCL) tumor subtype had decreased plasma levels of EVs bearing PD-L1, compared to those with Burkitt's lymphoma. CD40, CD40L and TNF-RII-expressing EVs showed a significant positive correlation with plasma levels of IL-10, CXCL13, sCD25, sTNF-RII and IL-18. Our results suggest that patients with AIDS-NHL have higher levels of EVs expressing PD-L1, CD40, CD40L or TNF-RII in circulation before cancer treatment and that levels of these EVs are associated with levels of biomarkers of microbial translocation and inflammation.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Acquired Immunodeficiency Syndrome*
B7-H1 Antigen
CD40 Antigens
CD40 Ligand
Extracellular Vesicles*
Humans
Lymphoma, AIDS-Related*
Receptors, Tumor Necrosis Factor, Type II

Substances

B7-H1 Antigen
CD274 protein, human
CD40 Antigens
Receptors, Tumor Necrosis Factor, Type II
CD40 Ligand

Abstract

Publication types

MeSH terms

Substances

Grants and funding