Enhanced anticancer efficacy of photodynamic therapy in combination with immunotherapy

Photodynamic therapy (PDT) is known to trigger immunogenic cell death (ICD), leading to an anticancer effect even in untreated metastatic cancer, a phenomenon called the “abscopal effect”. Furthermore, ICD induction activates an immune response, which may synergize with immunotherapy. The objective of our research was to evaluate the anticancer efficacy of combining PDT with immunotherapy. To assess in vivo anticancer efficacy and the abscopal effect, we implanted CT26 cells on both flanks of BALB/c mice. The mice were categorized into five different groups: 1) PBS, 2) immunotherapy alone, 3) PDT alone, 4) immunotherapy administered 3 days after PDT, and 5) immunotherapy administered immediately after PDT. The observed antitumor effects on the primary tumor followed this order: immunotherapy administered immediately after PDT > immunotherapy administered 3 days after PDT > PDT alone > immunotherapy alone > PBS. In metastatic tumors that were not directly treated, immunotherapy administered immediately after PDT was also the most effective. In conclusion, our study confirms that the combination of PDT with immunotherapy enhances anticancer efficacy against both primary and metastatic tumors. Additionally, administering immunotherapy immediately after PDT is more effective than delayed administration. •PDT induced an acute inflammatory response in cancers, leading to an ICD response.•PDT with immunotherapy showed better anticancer effects than either treatment alone.•PDT with immunotherapy demonstrated the ‘abscopal effect’ in metastatic tumors.•Immediate immunotherapy after PDT was more effective than when applied later.