13P - The impact of cortisol on immune cells and its effect on cancer-immune cells co-culture in a 3D spheroid of ovarian cancer

Abstract

BackgroundOvarian cancer (OC) is one of the deadliest gynaecologic cancers predominantly of the epithelial subtype (EOC). Despite advances in treatments, relapse and dissemination is very likely to occur after remission. The heterogenous nature and complex immunosuppressive environment of the tumour implicate a heterogenous clinical outcome and a key role for the immune system in the disease prognosis. Diagnosis and treatment of cancer is often a traumatic experience associated with mental and physical comorbidities, cortisol is released in response to stress and has a controversial role to either promote or suppress stress depending on its physiological environment. Strong evidence is showing that stress hormones can influence tumour biology. In this study, the impact of cortisol on splenocytes and T cells and immune-cancer interactions were explored to probe a mechanism for its action in OC. MethodsC57BL/6j mice were either subjected to chronic restraint stress for 2hours a day over a period of six weeks or left alone in their home cages (no stress group). Splenocytes were then extracted and first examined for DNA damage measured by immunofluorescence using phosphorylated γ-H2AX. Splenocytes were next co-cultured with ovarian spheroids for five days and spheroids size and splenocytes infiltration were compared against no stress group. The impact of acute stress on DNA damage was tested in vitro on T lymphocytes subjected to physiological concentration of cortisol for 2h. ResultsChronic stress significantly increased DNA damage in mouse splenocytes (p=0.0027). Ex vivo T lymphocytes exposed to cortisol also showed a significant increase in DNA damage (p=0.017). Furthermore, a significant increase in the size of spheroids co-cultured with splenocytes from stress group was observed (p=0.0213) and cortisol inhibited immune cell trafficking into the spheroids. ConclusionsIn conclusion, both chronic stress and acute exposure to cortisol can increase DNA damage in splenocytes and T lymphocytes reducing their infiltration into cancer spheroids. This data may have impact for patient with ovarian cancer experiencing extreme stress. Legal entity responsible for the studyThe author. FundingHas not received any funding. DisclosureThe author has declared no conflicts of interest.