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
2066 - Second-line (2L) real-world treatment (tx) patterns and outcomes in patients (pts) with advanced/metastatic non-small cell lung cancer (NSCLC) treated with first line (1L) immuno-oncology (IO) monotherapy (mono tx)
Presenter: Denis Talbot
Session: Poster Display session 1
Resources:
Abstract
5919 - Real-world effectiveness of nivolumab monotherapy after prior systemic therapy in advanced non-small cell lung cancer (NSCLC) in the United States
Presenter: David Stenehjem
Session: Poster Display session 1
Resources:
Abstract
3368 - Pembrolizumab as first-line treatment in NSCLC with PD-L1 ≥50%: Real life results from an all-comer population
Presenter: Nikolaj Frost
Session: Poster Display session 1
Resources:
Abstract
3775 - Patients with metastatic non-small cell lung cancer without molecular alterations or PD-L1 expression in Germany. Treatment and first outcome from the prospective German Registry Platform CRISP (AIO-TRK-0315)
Presenter: Frank Griesinger
Session: Poster Display session 1
Resources:
Abstract
3926 - Impact of second-line (2L) immune checkpoint inhibitors (ICIs) on the treatment (Tx) of advanced non-small cell lung cancer (NSCLC) in a UK centre: a REAL-Oncology analysis from the I-O Optimise initiative
Presenter: Michael Snee
Session: Poster Display session 1
Resources:
Abstract
5068 - First line pembrolizumab for NSCLC with PD-L1 TPS > 50% in a first French real life cohort
Presenter: Karim Amrane
Session: Poster Display session 1
Resources:
Abstract
1182 - Interstitial lung disease induced by immune-checkpoint inhibitors correlates with prognosis of advanced non-small-cell lung cancer patients
Presenter: Teppei Sugano
Session: Poster Display session 1
Resources:
Abstract
2297 - Phase II study to evaluate the peripheral blood mononuclear cell biomarker for nivolumab efficacy on previously treated non-small cell lung cancer subjects (NEJ029B: IMMUNITY-ONE)
Presenter: Yosuke Kawashima
Session: Poster Display session 1
Resources:
Abstract
2739 - Efficacy and safety of nintedanib + docetaxel in lung adenocarcinoma patients (pts) following treatment with immune checkpoint inhibitors (ICIs): Updated results of the ongoing non-interventional study (NIS) VARGADO (NCT02392455)
Presenter: Christian Grohe
Session: Poster Display session 1
Resources:
Abstract
1357 - Upfront atezolizumab chemoimmunotherapy-associated Immune-related adverse events in patients with advanced non-small cell lung cancer
Presenter: Francis Mogollon-Duffo
Session: Poster Display session 1
Resources:
Abstract