Stress exacerbates pancreatic cancer both directly and indirectly by creating an immunosuppressive environment

Abstract Background/Purpose Sympathetic nerve stimulation by stress exacerbates various solid tumors, including pancreatic cancer (PCa). The relationship between cancer and immunity has been suggested; however, there is limited information about the effects of nerve stimulation on immunity and cancer. We aimed to investigate the involvement of sympathetic nerve stimulation in immune cells and its effects on PCa using a restraint stress mouse model. Methods In the in vitro experiment, the mouse‐derived PCa cell line (LTPA) was cultured in a noradrenalin‐supplemented medium. In the in vivo experiment, mice were divided into non‐stress and stress groups. Results LTPA proliferated significantly more when cultured in a noradrenalin‐supplemented medium than in a normal medium. Flow cytometry analysis of blood immune cells revealed a significant decrease in B cells, T cells, and macrophages and a significant increase in myeloid‐derived suppressor cells (MDSCs) in the stress group. Furthermore, a significant increase in blood noradrenaline levels was observed in the stress group ( p < .01). In the PCa mice model, immune cells in the blood showed a similar trend, and the stress group had a poor prognosis. Furthermore, immunostaining at the tumor site showed that there was a lower number of B and T cells in the stress group. In addition, MDSCs were present at the tumor margins. Conclusion These results suggest that sympathetic nerve stimulation is not only directly involved in PCa growth but also exacerbates PCa by creating an immunosuppressive environment in the blood and tumor tissue.