Photodynamic therapy boosts anti-glioma immunity in mice: A dependence on the activities of T cells and complement C3

Abstract

Photodynamic therapy (PDT) involves the systemic administration of a tumor-specific photosensitizer and local irradiation of visible light, can generate highly cytotoxic molecular species in the tumor and kill malignant cells directly or by shutting down the tumor microvasculature. Collectively data show that anti-tumor immunity is an important mechanism that mediates the PDT-induced tumor-destroying effects in many types of cancers. However, it is unknown whether PDT also promotes anti-tumor immunity in gliomas in the central nervous system (CNS). Here we show that the PDT generates regional and systemic anti-tumor immunity in mice with G422 gliomas in the brain. The infiltration of immune cells and the release of inflammatory factors, such as TNF-α and IFN-γ, are increased in animals with G422 gliomas following PDT when compared with those without receiving PDT. The lymphocytes that are isolated from PDT-treated mice are able to induce anti-tumor immunity in nude mice. The anti-glioma immunity fostered by PDT is inhibited in complement C3 knockout mice and the nude mice indicate the requirement of the activities of complement C3 and T cells. Thus, T cells that produce cytokines, along with complement C3, may play crucial roles in mediating PDT-induced anti-glioma responses.

Photodynamic therapy induces an immune response against a bacterial pathogen

“…Significant neutrophilia was observed upon PDT treatment and was prevented by complement inhibition. The activation of the complement system in particular has emerged as a powerful mediator of PDT antitumor effects [27–29]. Complement not only acts as direct mediator of inflammation, but also stimulates cells to release secondary inflammatory mediators, including cytokines IL-1β, TNF-α, IL-6, IL-10, G-CSF, thromboxane, prostaglandins, leukotrienes, histamine and coagulation factors.…”

5-ALA Fluorescence in Native Pituitary Adenoma Cell Lines: Resection Control and Basis for Photodynamic Therapy (PDT)?

“…Li and colleagues demonstrated regional and systemic anti-tumor immunity in mice with intracranial G422 glioma xenografts. Infiltration of immune cells and the release of inflammatory 203 factors, such as TNF-α and IFN-γ, were increased following PDT when compared to 204 untreated animals [33]. …”

Responses of Cancer Cells Induced by Photodynamic Therapy

“…Lymphocytes isolated from PDT-treated animals were able to induce anti-tumor immunity in nude mice; however, the anti-glioma immunity fostered by PDT was inhibited in complement C3 knockout mice, indicating the requirement of the activities of complement C3 and T cells. T cells that produce cytokines, along with complement C3, may play crucial roles in mediating PDT-induced anti-glioma responses [84].…”