Poster Presentation Cancer Survivorship Conference 2023

Circadian disruption changes the inflammatory response to cancer in an organ-dependent manner in a mouse model of breast cancer.   (#167)

Adam K Walker 1 2 , Adam J Lawther 2 , Ni-Chun Chung 3 , Aeson Chang 3 , Alexandra I Ziegler 3 , Sophie Debs 4 , Erica K Sloan 3 , Andrew JK Phillips 5
  1. Discipline of Psychiatry and Mental Health, University of New South Wales, Sydney, NSW, Australia
  2. Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick, NSW, Australia
  3. Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia
  4. Schizophrenia Research Laboratory, Neuroscience Research Australia, RANDWICK, NSW, Australia
  5. Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, VIC, Australia

Inflammation is a hallmark of cancer and is linked to worse prognosis and side-effects such as depression, worse stress-coping ability, cognitive impairment, and peripheral neuropathy. This has led to attempts to develop anti-inflammatory interventions for these symptoms. One factor that can alter inflammatory responses and impair immune function is circadian disruption, which is also associated with cancer. However, there remains a limited understanding of how circadian disruption modulates cancer-induced inflammation, making it difficult to ascertain if anti-inflammatory strategies designed to treat cancer-related side-effects will be as efficacious in patients with circadian disruption. To explore this, we investigated the effect of circadian disruption on cancer-induced inflammation in an orthotopic mouse breast cancer model. Using a validated chronic jetlag protocol that advances the light-cycle by 8 ​h every 2 days to disrupt circadian rhythms, we found that circadian disruption alters cancer-induced inflammation in a tissue-specific manner, increasing inflammation in the body and brain while decreasing inflammation within the tumour tissue itself (p < 0.05 for all). Circadian disruption did not affect tumour burden (p > 0.05), suggesting that increased inflammation was not a result of increased cancer progression. Importantly, how cancer-induced inflammation was changed by circadian disruption differed depending on the organ that was investigated. Overall, these findings identify the importance of healthy circadian rhythms for limiting cancer-induced inflammation. Anti-inflammatory interventions designed to treat cancer-related symptoms may require remediation of circadian disruption to be most effective.