Surgical Inflammation Alters Immune Response to Intraoperative Photodynamic Therapy

Area of Science:

• Oncology
• Immunology
• Surgical Oncology

Background:

• Malignant pleural mesothelioma (MPM) is challenging to treat, often requiring multi-modality approaches.
• Photodynamic therapy (PDT) is an intraoperative option for MPM, but its interaction with surgical effects is unclear.
• Surgical cytoreduction is crucial for MPM but may influence residual disease response.

Purpose of the Study:

• To investigate the impact of surgical-induced inflammation on the efficacy of photodynamic therapy (PDT) in malignant pleural mesothelioma (MPM).
• To determine if combining surgical cytoreduction with PDT offers curative potential in preclinical models.
• To explore the immunological consequences of combining surgery and PDT for MPM.

Main Methods:

• Utilized a murine model of MPM with surgical debulking (60-90% tumor removal).
• Administered Photofrin-based photodynamic therapy (PDT) post-surgery.
• Employed a tumor incision (TI) model to assess the effect of surgical inflammation on PDT efficacy.
• Evaluated antitumor immunity transfer via splenocytes and CD8+ T cells.

Main Results:

• PDT combined with surgical debulking demonstrated long-term response and curative potential in MPM murine models.
• Surgical incisions alone did not affect acute PDT cytotoxicity.
• Surgically induced inflammation significantly limited the generation of antitumor immunity by PDT.
• Immune cells from mice treated with TI followed by PDT transferred less antitumor immunity compared to PDT alone.

Conclusions:

• Combining PDT with surgical cytoreduction enhances long-term outcomes for MPM compared to surgery alone.
• Surgically induced inflammation can impede the development of antitumor immunity stimulated by PDT.
• Strategies to mitigate surgical immunosuppression may improve outcomes for intraoperative combined modality treatments in MPM.