Effects of the photodynamic therapy fluence on the adaptive immune system

An inflammatory reaction is elicited as part of the normal healing process to an insult and in cases of pathogenic infection it has been shown to be vital for the generation of an effective adaptive immune response. Usually innate immune cells first sense the pathogens and orchestrate the ensuing response by directly fighting the pathogens and recruiting additional immune cells, such as antigen presenting cells (APCs), which in turn will activate cells of the adaptive immune system. This results in the clearance of the invading pathogen. In contrast to the beneficial effects of acute inflammation during establishment of anti-pathogenic immunity, little is known about the role of acute inflammation in induction of anti-tumor immunity. We took advantage of the observation that following photodynamic therapy (PDT) of mouse tumors an acute inflammatory reaction is induced, whose magnitude can be determined by the PDT dose. PDT is an FDA approved modality for the treatment of early and the palliation of advanced cancer disease. It relies on the activation of a photosensitizer after exposure to light of a certain wavelength and this results in the production of singlet oxygen, the main cytotoxic mediator in PDT. By employing two different PDT dose treatments that achieved high or low local inflammation, we examined if acute inflammatory response in a tumor setting could influence the generation of a tumor specific immune response. A strong tumor specific CD8+ T cell response was observed in the PDT induced high inflammation treatment, with those immune cells being able to fight establishment of tumors in lungs more effectively than immune cells from PDT induced low inflammation or control treated mice. An effective tumor specific memory response was only evident for immune responses elicited in environments of high inflammation. Furthermore, innate Gr1+ cells were instrumental in the development of an effective anti-tumor CD8 + immune response, since in their absence an effective anti-tumour response was not observed. Gr1+ cells were required to infiltrate the tumors in order to exert their immune "co-coordinating" properties, as mice defective in Gr1+ cell homing to peripheral tissues (CXCR2 -/-) elicited very weak CD8+ T cell response to tumor. Overall, Gr1+ cells seem to be vital mediators in an anti-tumor immune response.