Alteration of tumour response to radiation by interleukin-2 gene transfer

We have previously shown that BALB/c-derived EMT6 mammary tumours transfect ed with interleukin (IL)-2 have decreased hypoxia compared to parental tumo urs, due to increased vascularization. Since hypoxia is a critical factor i n the response of rumours to radiation treatment, we compared the radiation response of IL-2-transfected tumours to that of parental EMT6 tumours, Bec ause the IL-2 tumours have an altered host cell composition, which could af fect the interpretation of radiation sensitivity as measured by clonogenic cells, we employed flow cytometric analysis to determine the proportion of tumour cells vs host cells in each tumour type. Using this approach, we wer e able to correct the plating efficiency based on the number of actual tumo ur cells derived from rumours, making the comparison of the two types of tu mours possible. We also excluded the possibility that cytotoxic T-cells pre sent in EMT6/IL-2 tumours could influence the outcome of the clonogenic cel l survival assay, by demonstrating that the plating efficiency of cells der ived from EMT6/IL-2 tumours remained unchanged after depletion of Thy-1(+) cells. The in vivo radiation response results demonstrated that IL-2-transf ected rumours were more sensitive to radiation than parental EMT6 rumours. The hypoxic fraction of the EMT6/IL-2 tumours growing in vivo was markedly decreased relative to parental EMT6 tumours thus the increased sensitivity results from the increased vascularity we have previously observed in these rumours. These results indicate the potential therapeutic benefit of combi ning radiation and immunotherapy in the treatment of rumours, (C) 2000 Canc er Research Campaign.