Potential effects of the tumor microenvironment after BNCT: pro or antitumoral response and bystander effect in colorectal cancer cells

Abstract

Purpose: The aim of this work is to describe the influence of the tumor microenvironment (TME) after Boron Neutron Capture Therapy (BNCT) that could condition immune system response and bystander effects in colorectal cancer (CRC) treatment. Materials and methods: HT29 colorectal carcinoma cells were incubated with BPA (50ppm) and irradiated with neutrons in a mixed field. Cytosolic dsDNA was detected by immunofluorescence and IFNβ, Galectin-1, TGFβ1, IRF1, Nox1, and Nox5 expression by qPCR. Conditioned mediums (CM) from irradiated cells were used to study the bystander effect on cell migration and proliferation. Results: Cytosolic dsDNA and IFNβ increased in cells treated with BNCT. No change of Galectin-1 mRNA was observed in BNCT treated cells. IRF1 mRNA increased at 3 and 8Gy without BPA. Nox1 increased at 8Gy and Nox5 increased at 8Gy+BPA. CM of 8Gy+BPA induced cells migration of non-irradiated cells but had no effect on cell proliferation. Conclusions: TME alteration by BNCT could influence immune response. Cytosolic dsDNA induces IFNβ that could activate the cGAS-STING pathway, leading to anti-tumor responses. No changes in Galectin-1 could be also a positive response to BNCT while IRF1 seems to have no relation. The potential TGFβ1 increase and the persistence of NADPH oxidases induction represents long term cellular damage, affecting tissue protection and tumor sensitization. The bystander effect on cell migration demonstrate the importance of the impact of radiotherapy out of the field of irradiation.