Dataset Information

CD47 cross-dressing by extracellular vesicles expressing CD47 inhibits phagocytosis without transmitting cell death signals.

ABSTRACT: Transgenic CD47 overexpression is an encouraging approach to ameliorating xenograft rejection and alloresponses to pluripotent stem cells, and the efficacy correlates with the level of CD47 expression. However, CD47, upon ligation, also transmits signals leading to cell dysfunction or death, raising a concern that overexpressing CD47 could be harmful. Here, we unveiled an alternative source of cell surface CD47. We showed that extracellular vesicles, including exosomes, released from normal or tumor cells overexpressing CD47 (transgenic or native) can induce efficient CD47 cross-dressing on pig or human cells. Like the autogenous CD47, CD47 cross-dressed on cell surfaces is capable of interacting with SIRPα to inhibit phagocytosis. However, ligation of the autogenous, but not cross-dressed, CD47 induced cell death. Thus, CD47 cross-dressing provides an alternative source of cell surface CD47 that may elicit its anti-phagocytic function without transmitting harmful signals to the cells. CD47 cross-dressing also suggests a previously unidentified mechanism for tumor-induced immunosuppression. Our findings should help to further optimize the CD47 transgenic approach that may improve outcomes by minimizing the harmful effects of CD47 overexpression.

SUBMITTER: Li Y

PROVIDER: S-EPMC9714967 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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CD47 cross-dressing by extracellular vesicles expressing CD47 inhibits phagocytosis without transmitting cell death signals.

Li Yang Y Wu Yan Y Federzoni Elena A EA Wang Xiaodan X Dharmawan Andre A Hu Xiaoyi X Wang Hui H Hawley Robert J RJ Stevens Sean S Sykes Megan M Yang Yong-Guang YG Yang Yong-Guang YG

eLife 20221201

Transgenic CD47 overexpression is an encouraging approach to ameliorating xenograft rejection and alloresponses to pluripotent stem cells, and the efficacy correlates with the level of CD47 expression. However, CD47, upon ligation, also transmits signals leading to cell dysfunction or death, raising a concern that overexpressing CD47 could be harmful. Here, we unveiled an alternative source of cell surface CD47. We showed that extracellular vesicles, including exosomes, released from normal or t ...[more]

PMID: 36454036

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Project description:Cancer specific extracellular vesicles (EVs) are of significant clinical relevance, for instance programmed death ligand-1 (PD-L1) expressing EVs (PD-L1@EVs) have been shown to be ideal biomarker for non-invasive diagnosis of cancer and can predate the response of cancer patients to anti-PD-1/PD-L-1 immunotherapy. The development of sensitive and straightforward methods for detecting PD-L1@EVs can be a vital tool for non-invasive diagnosis of cancer. Most of the contemporary methods for EVs detection have limitations such as involvement of long and EV's loss prone isolation methods prior to detection or they have employed expensive antibodies and instruments to accomplish detection. Therefore, we designed an ultracentrifugation-free and antibody-free sensing assay for PD-L1@EV by integrating Titanium oxide (TiO2) coated magnetic beads (Fe3O4@TiO2) rapid capturing of EVs from undiluted serum with aptamers specificity and chemiluminescence (CL) sensitivity. To accomplish this we used Fe3O4@TiO2 beads to rapidly capture EVs from the undiluted patient serum and added biotin labelled PD-L1 aptamer to specifically recognize PD-L1@EVs. Later, added streptavidin-modified Alkaline phosphates (ALP) taking advantage of biotin-streptavidin strong binding. Addition of CDP-star, a chemiluminescent substrate of ALP, initiates the chemiluminiscense that was recorded using spectrophotometer. The sensing assay showed high sensitivity with limit of detection (LOD) as low as 2.584×105 EVs/mL and a wider linear correlation of CL intensity (a.u.) with the concentration of PD-L1@EVs from 105 to 108 EVs/mL. To examine the clinical utility of sensing assay we used undiluted serum samples from lung cancer patients and healthy individuals and successfully discern between healthy individuals and lung cancer patients. We are optimistic that the sensing assay can ameliorate our ability to be able to diagnose lung cancer non-invasively and can be helpful to predate the patient's response to anti-PD-1/PD-L1 immunotherapy.

Dataset Information

CD47 cross-dressing by extracellular vesicles expressing CD47 inhibits phagocytosis without transmitting cell death signals.

Publications

CD47 cross-dressing by extracellular vesicles expressing CD47 inhibits phagocytosis without transmitting cell death signals.

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