Metronomic Photodynamic Therapy With Immune Checkpoint Inhibitors Does Not Affect Nontarget Lesions

Immune checkpoint inhibitors (ICIs) have extended survival in various cancers, especially when combined with chemotherapy. This effect is thought to involve tumor-specific antigen release and T cell reactivation. The "abscopal effect," where radiation leads to tumor shrinkage at distant sites, may also be enhanced by ICIs, although this is not fully understood. Photodynamic therapy (PDT), a localized treatment, has shown potential for inducing abscopal effects, but no studies have investigated this in metronomic PDT (mPDT), which uses low fluence rates over extended periods. This study aimed to evaluate if mPDT exerts the abscopal effect and whether the addition of ICIs can enhance this effect.

Colon-26 tumor-bearing mice were treated with conventional (cPDT) or mPDT, with or without anti-PD-L1 antibodies. Tumor growth in target and nontarget lesions was measured, and immune cell infiltration was analyzed by flow cytometry.

When combined with anti-PD-L1, cPDT significantly reduced tumor size in nontarget lesions and increased the infiltration of CD4⁺, CD8⁺, and CD3⁺ cells in these areas. In contrast, mPDT did not elicit a comparable antitumor response or promote CD4⁺, CD8⁺, and CD3⁺ cell infiltration in nontarget lesions.

While cPDT combined with ICIs successfully reduced tumor size in nontarget lesion, mPDT did not, suggesting a limited capacity to induce systemic immune responses. Further research is needed to optimize mPDT for systemic cancer therapy.