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
3887 - First Real Life Data on Durvalumab after definitive concomitant ChemoRadiotherapy (cCRT) in unresectable Stage (St) III Non-Small Cell Lung Cancer (NSCLC) in France: Analysis of 591 patients (pts) enrolled in the French cohort (c) Temporary Authorization of Use (ATU)
Presenter: Virginie Avrillon
Session: Poster Display session 1
Resources:
Abstract
682 - EGFR Inhibitor Versus Chemotherapy as Adjuvant Treatment for Locally-advanced EGFR-mutant Non-Small Cell Lung Cancer
Presenter: Peng Xie
Session: Poster Display session 1
Resources:
Abstract
2509 - Afatinib in EGFR TKI-naïve patients with EGFR mutation-positive (EGFRm+) NSCLC: interim analysis of a Phase IIIb, multi-national, open-label study
Presenter: Filippo de Marinis
Session: Poster Display session 1
Resources:
Abstract
3300 - First-line ceritinib versus chemotherapy in patients (pts) with advanced ALK rearranged (ALK+) non-small cell lung cancer (NSCLC): ASCEND-4 Asian subgroup analysis
Presenter: Daniel SW Tan
Session: Poster Display session 1
Resources:
Abstract
2653 - A combined analysis of two Phase IIIb studies of afatinib in EGFR TKI-naïve patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC
Presenter: Filippo de Marinis
Session: Poster Display session 1
Resources:
Abstract
3663 - Impact of plasma EGFR mutation fractions on response to first generation tyrosine-kinase inhibitor in treatment of naïve non-small cell lung cancer patients
Presenter: Xiaohong Wang
Session: Poster Display session 1
Resources:
Abstract
5921 - Definition of an afatinib trough concentration threshold in the treatment of NSCLC
Presenter: Stephane Bouchet
Session: Poster Display session 1
Resources:
Abstract
2852 - A Phase Ib Trial of Neoadjuvant Chemoradiotherapy and Durvalumab(MEDI4736) for Potentially Resectable stage III Non-Small Cell Lung Cancer (NSCLC)
Presenter: Beung chul AHN
Session: Poster Display session 1
Resources:
Abstract
3273 - Low expression of Notch1 and combined Notch1/HES1 are associated with adverse survival factor for limited stage small cell lung cancer
Presenter: Jinsoo Lee
Session: Poster Display session 1
Resources:
Abstract
5141 - Mutational profiling of tumor tissue and sequential plasma illustrates emergent clones during treatment in late stage small cell lung cancer (SCLC)
Presenter: Stephanie Yaung
Session: Poster Display session 1
Resources:
Abstract