Sean Krivitsky, Class of 2026

Stress is a common response many experience amidst various physical, emotional, or psychological challenges. Beyond its significant short-term impacts, chronic stress has been demonstrated to impact cognitive function as well as the health of various systems within the body, including the immune system. Cancer patients in particular often fall victim to chronic stress, which, in turn, has been associated with greater instances of cancer metastasis, or spread through the body, and poorer cancer patient prognosis. This is because stress has been suggested to induce pro-metastatic properties of immune cells called neutrophils, specifically their formation of neutrophil extracellular traps (NETs), which are webs of cellular contents. Recently, research collaborators at Cold Spring Harbor Laboratory and Stony Brook University sought to elucidate the mechanisms underlying these effects on cancer patients resulting from increased release of glucocorticoid (GC) stress hormones. 

The researchers used mouse models, which were exposed to chronic unpredictable mild stress (CUMS), including physical restraint, to stimulate GC release and test the effects of chronic stress on the disease progression of breast cancer, pancreatic ductal adenocarcinoma (PDA), and lung cancer metastasis models. They monitored the stress levels of mice and employed tumor tissue analysis, in vivo neutrophil assays, and DNA-protein interaction tests to describe the impact of stress on cancer progression. This testing revealed that stress conditions modeled after cancer patients led to increased levels of cancer metastasis and decreased immune activity within the tumor microenvironment. Further analysis revealed that these effects were largely driven by GC receptor signaling on neutrophils, which increased the percentage presence of neutrophils and increased spontaneous NET formation. Targeting these NETs by elimination of GC receptors on neutrophils helped rescue cancer metastases.

Ultimately, this study reveals key information on a less frequently considered factor in the progression and treatment process of cancer. Chronic stress frequently impacts cancer patients given the significant difficulties associated with the obtaining of cancer treatments and their associated large medical bills. Given the revealed impact of chronic stress on NET formation and resultant promotion of cancer metastasis and progression, the importance of a multifactor approach to cancer treatment is emphasized, particularly to include a focus on stress-induced detriments to cancer treatment. Targeting GC receptors and neutrophils will likely prove to be a key method for improving overall cancer patient prognosis.

Figure 1: Individual experiencing stress

Works Cited:

[1] X.-Y. He, et al., Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment. Cancer Cell 42 (2024). doi:10.1016/j.ccell.2024.01.013

[2] Image retrieved from: https://commons.wikimedia.org/wiki/File:Human_stress.jpg