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Activated T cell extracellular vesicle DNA transfer enhances antigen presentation and anti-tumor immunity

ABSTRACT: Antigen processing and presentation (APP) is essential for adaptive immunosurveillance. We uncover a mechanism whereby activated T cell-derived extracellular vesicles (AT EVs ) drive a positive feedback loop that enhances antigen presentation and immune responses in normal physiology and cancer. AT EV -induced immunogenicity relies on extracellular vesicular double-stranded DNA (EV DNA ), 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 AT EVs disrupts the nuclear envelope of recipient cells, facilitating intranuclear transfer and subsequent transient expression of EV DNA encoding APP genes. DNase treatment removes most AT-EV DNA , abrogating APP upregulation and thus T cell activation and recruitment to tumors. Notably, AT EVs 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 AT EVs which boosts APP and anti- tumor immunity while limiting autoimmunity.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: henrik molina

LAB HEAD: David Lyden

PROVIDER: PXD075986 | Pride | 2026-03-23

REPOSITORIES: Pride

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			Action	DRS
	MS227362QEHF_Mengying_Lyden_Activated_T-1.raw	Raw
	MS227362QEHF_Mengying_Lyden_Activated_T-2.raw	Raw
	MS227362QEHF_Mengying_Lyden_naive_T-1.raw	Raw
	MS227362QEHF_Mengying_Lyden_naive_T-2.raw	Raw
	MS227362_Mengying_Lyden.xlsx	Xlsx

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