Astatine-211 injury induces an immunostimulatory melanoma-cell state and promotes systemic antitumor immunity

Astatine-211–injured B16F10 melanoma cells (1 MBq/mL) suppress pulmonary metastasis in C57BL/6J mice and induce tumor-reactive interferon-gamma responses and antibodies.

• Why it matters: Targeted alpha therapy is usually judged by dose and direct killing, but whether alpha-injured tumor cells can prime systemic antitumor immunity is unclear.
• What they did: B16F10 cells were exposed ex vivo to 211At, etoposide, or ultraviolet irradiation to ~40% viable-cell counts at 24 hours, then used for prophylactic vaccination before intravenous tumor challenge. Transcriptomics showed enrichment of type I interferon, inflammatory, and chemokine signatures, with DNA damage markers (gammaH2AX), G2/M arrest, ROS, cytosolic double-stranded DNA, and senescence-like changes.
• The result: STING inhibition in vivo attenuated the antimetastatic effect, supporting that 211At injury generates a DNA-damage–linked immunostimulatory tumor-cell state that enables immune protection.