Cyclophosphamide enhances the release of tumor exosomes that elicit a specific immune response in vivo in a murine T-cell lymphoma

COCOZZA F; MENAY F; TSACALIAN R; ELISEI A; SAMPEDRO P; SORIA I; WALDNER C; GRAVISACO MJ; MONGINI C

VACCINE

ELSEVIER SCI LTD

Lugar: Amsterdam; Año: 2019

0264-410X

Exosomes are 60?150 nm small extracellular vesicles (EVs) released by most cells. Tumor-cell-derivedexosomes, used as a vaccine, elicit a specific cytotoxic response against tumor cells, usually with a greaterimmunogenicity than tumor-cell lysates. However, the number of exosomes isolated from culture cells islimited. In recent studies, it was observed that cells respond to different stressor stimuli such as cytotoxicdrugs, hypoxia, acidosis, or radiation by increasing the release of EVs.In this study, using the murine LBC T-cell lymphoma, we found that cyclophosphamide significantlyincreased EVs yield. These EVs express exosome marker proteins such as TSG-101, CD9, CD81, andCD63. Furthermore, similar humoral and cellular immune responses were induced in vivo by EVs isolatedfrom LBC-tumor cells whether they were grown under normal culture conditions (EVs C) or in the presence of cyclophosphamide (EVs CTX). Mice vaccinated either with EVs C or EVs CTX were similarly protected against an intraperitoneal challenge with LBC tumor cells. CD4+ and CD8+ IFN-c secreting cellswere induced in immunized mice and a specific cytotoxic cellular immune response was elicitedin vitro. These results demonstrate that a Th1 response was induced by immunization with the EVs.Our findings suggest that treatment of tumor cells with cyclophosphamide is a useful method to enhancethe secretion of EVs in sensitive cell lines without altering their antitumor properties and thus may beused to produce antigens for future design of cancer vaccines. 2