Immunogenic and systemic antitumor responses induced by photodynamic therapy: a systematic review of the abscopal effect

Photodynamic therapy (PDT) is a light-activated treatment that induces tumor cell death through the production of reactive oxygen species (ROS). There is emerging evidence that PDT can also elicit systemic antitumor immunity (abscopal effect) through the mechanisms of immunogenic cell death and immune reprogramming. The aim of this review was to systematically evaluate preclinical evidence of the abscopal and systemic immune responses induced by PDT. Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines, PubMed, Scopus, Web of Science, and Embase were searched up to September 2025. Eligible studies included animal models assessing distant tumor regression or systemic immune activation following PDT, with or without combination therapies. Twenty-four preclinical studies met the inclusion criteria. PDT consistently induced local tumor regression and immune activation, evidenced by damage-associated molecular pattern release, calreticulin exposure, and cytotoxic CD8-positive T lymphocyte infiltration. Several studies demonstrated clear abscopal effects, particularly when PDT was combined with programmed cell death protein-1/programmed death ligand 1 blockade or adjuvants. Reported cytokine upregulation, including interleukin-6, interferon-gamma, and tumor necrosis factor-alpha, confirmed robust systemic immune activation. Preclinical and early clinical studies suggested that PDT could be used to induce systemic, immune-mediated tumor control, similar to the abscopal effect. Optimizing treatment parameters and combination with immunotherapies may allow PDT to develop from a local, cytotoxic treatment to a systemic cancer immunotherapy.