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Updated: Aug 27, 2025

In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
Published on: September 23, 2021
Extracellular vesicle-based checkpoint regulation and immune state in cancer
Keywan Mortezaee1, Jamal Majidpoor2
1Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran. keywan987@yahoo.com.
Abstract:
Tumor cells exploit several mechanisms for hijacking an immunosuppressive tumor ecosystem in order to evade immune surveillance and to progress toward metastasis. Equipment of extracellular vesicles (EVs) with checkpoints is an example of cancer control over anti-tumor responses from immune system. Programmed death-ligand 1 (PD-L1) is a checkpoint highly expressed in a tumor at progressive stage. Interactions between PD-L1 with its receptor programmed death-1 receptor (PD-1) expressed on T cells will block the effector function of CD8+ T cells, known as one of the most important defensive cells against cancer. Evaluation of circulatory exosomal PD-L1 can be a prognostic biomarker in tumor diagnosis and responses to the immune checkpoint inhibitor (ICI) therapy, and can be considered as a tool in clinical practice for exploiting personalized therapy. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is also a checkpoint that its engagement with CD80/CD86 expressed on antigen-presenting cells (APCs), such as dendritic cells (DCs) hamper the priming phase of CD4+ and CD8+ T cells. Harvesting EVs from tumor and their modification with desired anti-checkpoint antibodies can be a promising strategy in cancer immunotherapy. The aim of this review is to discuss about EV roles in checkpoint regulation, cancer diagnosis and ICI responses, and to survey possible application of such vesicles in cancer immunotherapy.
Insights
Extracellular vesicles (EVs) carrying immune checkpoints like PD-L1 can suppress anti-tumor immunity. Evaluating exosomal PD-L1 may aid cancer diagnosis and guide personalized immunotherapy.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Tumor cells create an immunosuppressive environment to evade immune detection and promote metastasis.
- Extracellular vesicles (EVs) are utilized by cancer cells to regulate anti-tumor immune responses.
- Immune checkpoints, such as PD-L1 and CTLA-4, play a critical role in tumor immune evasion.
Purpose of the Study:
- To review the role of EVs in regulating immune checkpoints within the tumor microenvironment.
- To explore the potential of EVs as biomarkers for cancer diagnosis and response to immune checkpoint inhibitor (ICI) therapy.
- To discuss the application of EVs in developing novel cancer immunotherapies.
Main Methods:
- Literature review focusing on extracellular vesicles, immune checkpoints (PD-L1, CTLA-4), and cancer immunotherapy.
- Analysis of the mechanisms by which EVs mediate immune suppression.
- Survey of current and potential clinical applications of EVs in oncology.
Main Results:
- PD-L1 on EVs can inhibit CD8+ T cell function, contributing to immune evasion.
- Circulating exosomal PD-L1 shows promise as a prognostic biomarker for cancer diagnosis and ICI therapy response.
- CTLA-4 interaction with APCs, modulated by EVs, can impair T cell priming.
Conclusions:
- EVs are key players in immune checkpoint regulation and tumor progression.
- Exosomal PD-L1 evaluation offers potential for personalized cancer treatment strategies.
- Engineered EVs hold significant promise for advancing cancer immunotherapy.
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