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Systemic immunosuppression induced by peritoneal photodynamic therapy
C J Jolles1, M J Ott, R C Straight
1Division of Gynecologic Oncology, University of Utah School of Medicine, Salt Lake City.
Abstract:
Although photodynamic therapy is being used increasingly for the diagnosis and treatment of human cancer, its effect on immune responses has received little attention. This aspect was examined in a murine model. Mice given peritoneal photodynamic therapy had markedly decreased contact hypersensitivity responsiveness, not observed with cutaneous photodynamic therapy. The immunosuppression was systemic, because contact hypersensitivity was depressed at distal, unirradiated sites. Photodynamic therapy induced adoptively transferable cells that inhibited contact hypersensitivity responses in naive mice. The immunosuppression was reversible, but persisted for 3 weeks after photodynamic therapy. An acute-phase response characterized by leukocytosis and elevated serum amyloid P levels was observed in mice given photodynamic therapy but not in mice treated with either laser or dye alone. These data suggest a link between the acute-phase response and immunosuppression. Thus, although photodynamic therapy shows promise in cancer treatment, the induction of decreased systemic immunoresponsiveness is an important observation with potentially detrimental consequences.
Insights
Photodynamic therapy (PDT) can suppress the immune system, particularly when administered peritoneally. This immunosuppression is systemic, linked to an acute-phase response, and may have implications for cancer treatment.
Area of Science:
- Immunology
- Oncology
- Photochemistry
Background:
- Photodynamic therapy (PDT) is increasingly used for cancer diagnosis and treatment.
- The impact of PDT on immune responses remains under-investigated.
- Understanding PDT's immunomodulatory effects is crucial for optimizing cancer therapy.
Purpose of the Study:
- To investigate the effects of photodynamic therapy on immune responses in a murine model.
- To determine if PDT-induced immunosuppression is local or systemic.
- To explore the relationship between PDT, acute-phase response, and immune function.
Main Methods:
- Murine model used to assess contact hypersensitivity (CHS) responsiveness after photodynamic therapy (PDT).
- Comparison of peritoneal PDT versus cutaneous PDT effects.
- Adoptive transfer experiments to identify immunosuppressive cells.
- Monitoring of acute-phase response markers (leukocytosis, serum amyloid P).
Main Results:
- Peritoneal PDT markedly decreased contact hypersensitivity responsiveness, unlike cutaneous PDT.
- Immunosuppression was systemic, affecting unirradiated sites.
- Adoptively transferable cells from PDT-treated mice inhibited CHS responses.
- PDT induced an acute-phase response, including leukocytosis and elevated serum amyloid P.
- Immunosuppression was reversible but persisted for 3 weeks.
Conclusions:
- Photodynamic therapy, especially when delivered peritoneally, can induce significant systemic immunosuppression.
- A link exists between the acute-phase response and PDT-induced immunosuppression.
- The potential for detrimental consequences due to decreased immunoresponsiveness warrants consideration in cancer treatment strategies involving PDT.