Sleep restriction increased murine melanoma lung metastasis formation by reducing the number of cytotoxic cells and inducing a suppressive tumor microenvironment

Abstract

Sleep restriction (SR) is an increasing condition in the modern society, and it leads to higher production of stress hormones in humans and rodents. These hormones, at high concentrations, can change many aspects of the immune system, including the production of antibodies, cytokine profiles, cell trafficking, among others, providing the development of diseases, like cancer. The aim of this study was to analyze the effects of sleep restriction (SR) in the development of melanoma lung metastases in male C57BL/6. To this, mice were inoculated with B16F10 in the lateral tail vein (day 0). In the next day (day 1), mice were submitted to sleep restriction (SR) by the modified multiple platforms method. At days 2, 7, 14 and 21, control and SR mice (5 per day, per group) were euthanized, the lung metastases were counted and tumor microenvironment cells were analyzed by flow cytometry. Results shown that, in SR mice, tumor appeared earlier and more lung metastatic colonies were formed. Cytotoxic NK and CD8 T cells were reduced and the ratio between effector and regulatory T cells were smaller in sleep restricted mice in day 14. The same results were observed when the ratio IFN-gamma/Il-4 and IFN-gamma/IL-10 were analyzed. Together, these data suggest that sleep restriction induced a suppressive tumor microenvironment and impaired anti- tumor effector cells infiltration, thus favoring rapid tumor installation and growth.