Whole-Body Low Dose Irradiation Promotes the Efficacy of Conventional Radiotherapy for Cancer and Possible Mechanisms

Abstract

The purpose of the present study was to explore the possibility of establishing cancer radiotherapy protocols that could promote treatment efficacy at a reduced radiation dose. Mouse models of melanoma (B16) and Lewis lung carcinoma (LLC) were used in the experiments. Conventional local radiotherapy was combined with low dose whole-body irradiation (LDWBI) in the presence or absence of gene therapy by intratumor injection of a recombinant plasmid Egr-mIL-18-B7.1 (E18B). After a number of trials with different combinations it was found that a protocol of 2-week treatment with 2 × (E18B + 2 Gy + 0.075 Gy × 2) was found to be able to promote treatment efficacy at a reduced radiation dose. In this protocol local irradiation with 2Gy was administered 24h after intratumor injection of 10 μg of the plasmid E18B followed by LDWBI with 0.075 Gy every other day for 2 sessions in 1 week, and the procedure was repeated for another week. When this combined treatment was compared with conventional radiotherapy, i.e., 2Gy every other day 3 times in one week repeated for 2 weeks, the treatment efficacy was improved, as judged by increased average survival rate, reduced mean tumor weight, reduced pulmonary metastasis and suppressed intratumor capillary growth with a 2/3 reduction of radiation dose. Immunologic studies showed stimulated natural killer (NK) and cytotoxic T lymphocyte (CTL) activity as well as increased interferon-γ (IFN-γ) secretion in this combined treatment group as compared with the group receiving local treatment alone. It is suggested that up-regulation of host anticancer immunity by LDWBI and the initiation of expression of immune genes by both the local large dose and LDWBI are important factors in the realization of improved cancer control.