Abstract 4270
Background
Ovarian 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.
Methods
C57BL/6j mice were either subjected to chronic restraint stress for 2 hours 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.
Results
Chronic 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.
Conclusions
In 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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.
Resources from the same session
4526 - Long-term outcome of neoadjuvant tyrosine kinase inhibitors (TKI) in locally advanced dermatofibrosarcoma protuberans (DFSP)
Presenter: Jessica Beaziz
Session: Poster Display session 1
Resources:
Abstract
1214 - Neo-adjuvant (NA) Imatinib for gastrointestinal stromal tumours (GISTs): What is the optimal length of treatment?
Presenter: Tom Wilson
Session: Poster Display session 1
Resources:
Abstract
2690 - Gastrointestinal Stromal Tumours (GIST) in adolescents and young adults (AYA)
Presenter: Nikki Ijzerman
Session: Poster Display session 1
Resources:
Abstract
4558 - Radiomics improves response evaluation for desmoid tumors treated with chemotherapy
Presenter: Amandine Crombe
Session: Poster Display session 1
Resources:
Abstract
2751 - Radiomics of gastrointestinal stromal tumors; risk classification based on computed tomography images – a pilot study
Presenter: Milea Timbergen
Session: Poster Display session 1
Resources:
Abstract
2737 - Differentiating well-differentiated liposarcomas from lipomas using a radiomics approach
Presenter: Melissa Vos
Session: Poster Display session 1
Resources:
Abstract
1282 - The immune landscape of chondrosarcoma reveals an anti inflammatory environment
Presenter: Iseulys Richert
Session: Poster Display session 1
Resources:
Abstract
1572 - Impact of Immunotherapy and Targeted Therapy on Tumor Growth Rate in Sarcoma
Presenter: Esmail Al-ezzi
Session: Poster Display session 1
Resources:
Abstract
3414 - DNA methylation profiles of angiosarcoma subtypes.
Presenter: Marije Weidema
Session: Poster Display session 1
Resources:
Abstract
3411 - Prognostic significance of circulating PD-1, PD-L1, pan-BTN3As and BTN3A1 in patients with metastatic gastrointestinal stromal tumors (mGISTs)
Presenter: Daniele Fanale
Session: Poster Display session 1
Resources:
Abstract