A study led by researchers from Weill Cornell Medicine has found that extracellular vesicles released by activated T cells contain DNA fragments that can be transferred to other immune cells and tumor cells.
In preclinical models of three types of cancer, this process was associated with slowed tumor growth and increased immune cell infiltration.
Mechanism
Activated T cells secrete nanoscale membrane-bound particles (extracellular vesicles) that carry DNA fragments. The DNA is enriched for immune-related genes and is located primarily on the vesicle surface. An enzyme on the vesicle surface facilitates the transfer of DNA into the nuclei of recipient cells, where it is transiently expressed.
The vesicles travel to lymph nodes, the spleen, and other immune centers, where they are preferentially taken up by antigen-presenting cells such as dendritic cells. This process enhances T-cell priming and broader immune activation. Additionally, the vesicle-associated DNA can enter tumor cells, potentially counteracting immune suppression and restoring tumor visibility to the immune system.
Preclinical Findings
In mouse models of glioblastoma, pancreatic cancer, and triple-negative breast cancer—three types of cancer described as immunologically silent—infusion of DNA-carrying vesicles from activated T cells was associated with:
- Slowed tumor growth
- Increased immune cell infiltration into tumors
The vesicles were taken up by both antigen-presenting cells and tumor cells. The approach was tested alone and in combination with existing immunotherapy.
"The vesicles could serve as a natural, non-viral platform for transient gene delivery."
Potential Applications
Researchers have suggested that these vesicles could serve as a natural, non-viral platform for transient gene delivery. The approach may be combined with existing immunotherapies to treat certain cancers.
Funding and Disclosures
The research was supported by the National Institutes of Health, the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the Thompson Family Foundation, the Children's Cancer and Blood Foundation, and other organizations. Some authors maintain relationships with external organizations; disclosures are publicly available.