Light power density governs local and systemic responses to photodynamic therapy

At the same light dose (J/cm2), photodynamic therapy power density (mW/cm2) determines whether distant unirradiated tumors are suppressed, linked to sustained versus reduced 1O2 and perfusion.

• Why it matters: Systemic antitumor effects of PDT are often attributed to immunogenic cell death and soluble DAMPs, but it is unclear whether the light delivery parameter itself governs responses at distant sites.
• What they did: The study compared low versus high power density PDT while keeping light dose constant, measuring tumor 1O2 generation, tumor perfusion, PD-L1 expression, soluble DAMPs in serum, and protein cargo in circulating small extracellular vesicles (sEVs).
• The result: Low power density sustained 1O2, preserved perfusion, and suppressed both irradiated and unirradiated tumors, while high power density reduced 1O2 and perfusion and increased PD-L1 in unirradiated tumors without growth inhibition; soluble DAMPs were unchanged but sEV cargo differed, suggesting sEVs may mediate systemic effects.

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