Psychology and Physiology: The Impact of Chronic Stress on Ovarian Cancer
Living through cancer can be a stressful experience for many patients as they confront uncertainties surrounding treatment outcomes and life expectancy. The experience can be particularly challenging for some patients with ovarian cancer, who face a five-year relative survival rate of just over 50%.
Chronic stress—defined as stress that persists for many weeks, months, or longer—not only lowers quality of life for many patients but can even have physiological impacts that worsen prognosis.
At two recent conferences organized by the American Association for Cancer Research (AACR), researchers reported new findings that expand our understanding of the relationship among chronic stress, depression, and disease progression in patients with ovarian cancer.
How Chronic Stress Impacts the Brains of Patients With Ovarian Cancer
At the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity, Luinet Melendez-Rodriguez, a PhD candidate at Ponce Health Sciences University in Puerto Rico, shared new insights into how chronic stress might impact the brain.
Prior studies have found that patients with ovarian cancer have heightened levels of anxiety and depression, with one analysis finding their risk to be more than three times that of the general population. Building on this knowledge, Melendez-Rodriguez and colleagues hypothesized that chronic stress might change the brain in a way that increases the patient’s susceptibility to depression.
To model the impact of chronic stress, the researchers exposed mice with ovarian tumors to daily stress for four weeks. They observed that chronically stressed mice exhibited accelerated tumor growth and higher systemic inflammation, as measured by increased levels of circulating cytokines. In the central nervous system, they found disruptions to the blood-brain barrier, which Melendez-Rodriguez noted could make the brain permeable to inflammatory cytokines.
Consistent with this, they observed hallmarks of neuroinflammation in the brains of chronically stressed mice, namely higher levels of inflammatory microglia and cytokines and reduced levels of brain-derived neurotrophic factor (BDNF), a marker of neuronal health. Reduced BDNF levels are associated with many neuronal diseases, including depression. These results indicated that chronic stress may have a detrimental effect on brain health in patients with ovarian cancer, said Melendez-Rodriguez.
Moreover, the researchers found that chronic stress led to neuroinflammation and impaired stress responses within the hippocampus, the region of the brain that regulates emotion. These effects were similar to “the type of changes you would see in a brain primed for depressive-like behaviors,” Melendez-Rodriguez said.
She explained that identifying these neurological and immunological changes is a first step towards a better understanding of the mechanisms underlying depression in patients with ovarian cancer.
How Chronic Stress Drives Ovarian Cancer Progression
At the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer, Yadiel A. Rivera-López, also a PhD candidate at Ponce Health Sciences University, shared additional insights into the physiological impacts of chronic stress, focusing on how it affects myeloid-derived suppressor cells (MDSCs), a type of immune cell that can suppress antitumor immune responses.
Using the same animal model that Melendez-Rodriguez used in her studies, Rivera-López and colleagues found that chronic stress was associated with increased infiltration of MDSCs into the ovarian tumor microenvironment, as well as into the bone marrow. These mice also had higher markers of MDSC activation and inflammation in the blood, as well as fewer T cells in the tumor microenvironment, suggesting immune suppression.
To investigate the specific pathways at play, Rivera-López and colleagues isolated MDSCs and ovarian cancer cells from mice and exposed each cell type to stress hormones. In both cases, they found that exposure to stress hormones activated the Notch signaling pathway, which is known to suppress immune activity.
Studies have linked increased infiltration of MDSCs into ovarian tumors to worse outcomes in patients, but there had been limited data on the impact of chronic stress and subsequent stress hormone release on MDSCs, Rivera-López noted.
The results he presented suggest that chronic stress may induce suppression of antitumor immune activity through activation of MDSCs and Notch signaling, offering a potential explanation for why chronic stress is associated with ovarian cancer progression and poor outcomes in patients.
Together, the findings from these two studies provide new insights into the physiological impacts of chronic stress and lay the foundation for potential therapeutic interventions to improve the prognosis of the many patients who suffer from chronic stress.
