Good news! Cancer is history (soon)!
"Activated immune cells secrete tiny capsules bearing DNA that can enter other immune and tumor cells to stimulate the body’s defense systems, according to a study ...
The discovery extends the scientific understanding of the immune system, identifies a new strategy for boosting immunity against cancers and potentially offers a new tool for delivering genetic payloads to other cells. ...
In the new study ... the researchers discovered that [extracellular] vesicles secreted by activated T cells – major weapons of the immune system – carry DNA that enters immune cells and nearby tumor cells to enhance the immune response against the tumor.
Preclinical experiments showed that this vesicle-associated DNA could be useful therapeutically, boosting T cell attacks against tumors that otherwise evoke little or no immune response. ..."
From the highlights and abstract:
"Highlights
• Activated T cells secrete abundant extracellular vesicular DNA (AT-EVDNA)
• AT-EVDNA is mainly from newly made genomic DNA rich in immune-related gene content
• ATEVs boost antigen presentation via EVDNA intranuclear transfer aided by granzyme B
• ATEVs act as acellular immunotherapy to overcome tumor immune evasion
Summary
Antigen processing and presentation (APP) is essential for adaptive immunosurveillance.
We uncover a mechanism whereby activated T cell-derived extracellular vesicles (ATEVs) drive a positive feedback loop that enhances antigen presentation and immune responses in normal physiology and cancer.
ATEV-induced immunogenicity relies on extracellular vesicular double-stranded DNA (EVDNA), which is notably abundant and primarily composed of genomic DNA enriched in immune-related genes, including those encoding APP machinery.
Mechanistically, granzyme B (Gzmb) packaged by ATEVs disrupts the nuclear envelope of recipient cells, facilitating intranuclear transfer and subsequent transient expression of EVDNA encoding APP genes.
DNase treatment removes most AT-EVDNA, abrogating APP upregulation and thus T cell activation and recruitment to tumors.
Notably, ATEVs hold promise as an acellular immunotherapy, restoring APP and synergizing with checkpoint blockade in immunotherapy-refractory tumors. Collectively, our findings uncover a mechanism of transient, non-viral gene delivery by ATEVs that boosts APP and anti-tumor immunity while limiting autoimmunity."
Activated T cell extracellular vesicle DNA transfer enhances antigen presentation and anti-tumor immunity (open access)
Graphical abstract
