Radiation Immune Modulation Therapy of Glioma

Since Roentgens discovery of the X-rays 1895, radiation therapy (RT) has been one of the most successful modalities used to treat cancer (Rontgen 1995). The experimental radiation treatment of glioma, however, took place first in 1938 (Bailey & Brunschwig 1938). Since then advances in radiation technology have expanded the role and value of using ionizing radiation in diagnosis, imaging and therapy of glioma. But despite substantial technical improvements in the current treatment modalities the survival rate for glioma patients is still very low (Barnholtz-Sloan, et al. 2007 ). Although the recently addition of temozolomide to conventional fractionated radiotherapy for newly diagnosed glioblastoma has resulted in an increased time of survival (Stupp, et al. 2005). Immunotherapy utilizes the fact that the immune system has a potential to react against tumour antigens and that this can result in immunological control of the tumour. There is an increasing body of evidence that the activation of cytotoxic T-lymphocytes (CTL) has a positive effect on the long-term survival of cancer patients receiving traditional therapies such as surgery, chemoor radiation-therapy (Nakano 2001; Prall 2004; L. Zhang, et al. 2003). It has been clearly demonstrated that tumour immune reactivity is of importance in treatment of several types of tumours (Shankar & Salgaller 2000). The immune response to glioma is primarily a result of the cell-killing function by the activated cytotoxic T cells (CTL). The aim of vaccination regimes is to enhance the effectors functions of CTL and the number of lymphoid cells within the glioma. But even if immune therapy cause large populations of lymphocytes to enter CNS tumours, total eradication of the glioma do not occur. This is partly due to the immunosuppressive factors produced by the glioma, which result in non-functioning CTL (Roszman, et al. 1991). Traditional fractionated radiation therapy decrease the number of radiation sensitive T cells and damping the immune response of immunotherapy. Thus the interest in combining radiation therapy and immunotherapy has so far been very sparse. The use of sterotactic techniques with single radiation exposure or hypo-fractionated radiation therapy, however, does modulate the immune response and increases the therapeutic outcome (Lee, et al. 2009; Wersäll, et al. 2006). This radioimmuno modulatory effect of radiation opens for a new approach in glioma therapy by the combination of radiationand immune-therapy. Currently, there is a growing interest in combining radiation with other kinds of therapy, of which some are immunotherapy, to treat a broad range of malignancies (Chakraborty, et al.