Tumor-derived extracellular vesicles in antitumor immunity and response to radiotherapy

Tumor-derived extracellular vesicles (tdEVs) are emerging as both circulating biomarkers and active mediators of tumor–immune communication. This presentation will explore these complementary roles in the context of radiotherapy.

The first part will focus on tdEVs as biomarkers of disease burden and treatment response. In oligorecurrent hormone-sensitive prostate cancer, low pre-treatment levels of PSMA-positive tdEVs were associated with prolonged disease control and greater benefit from stereotactic ablative radiotherapy (SABR), supporting their potential use for risk stratification and treatment selection.

The second part will examine how radiotherapy alters tdEV biology and antitumor immunity. Radiation increases tdEV release and trafficking to lymphoid organs, where tdEVs can suppress CD8 T-cell activity. Proteomic and functional studies identified B7-H3 as a key determinant of tdEV-mediated immune evasion after irradiation. Blockade of B7H3 in combination with radiation promotes systemic antitumor immunity and distant tumor control.

Together, these findings position tdEVs as both biomarkers of radiotherapy response and therapeutic targets for enhancing radiation-induced antitumor immunity.