The Cancer-Immune Dialogue in the Context of Stress

Key Authors and Affiliations

Stress does not directly affect cancer incidence but influences cancer evolution, dissemination, and treatment outcomes.
Stress triggers neuroendocrine changes affecting malignant cells, stromal cells, and immune cells in the tumor microenvironment.
Stress-induced molecules, termed SAIMs, reshape anti-tumor responses.
Stress affects systemic metabolism and gut microbiota, indirectly influencing anti-tumor immunity.
The complex interactions between stress, cancer, and immune responses have therapeutic implications.

Historically, the separation of body and mind in Western culture.
Recent acknowledgment of the interconnectedness of mental and physical health.
Cancer is not solely a cell-autonomous disease; immune surveillance and neuroendocrine-immune interactions are critical.
Neuroendocrine and immune systems extensively communicate, maintaining tissue homeostasis and minimizing disease manifestation.
Tumors are often innervated and infiltrated by immune cells, influencing cancer progression and therapeutic outcomes.

Stress and Cancer Outcomes: Anxiety and depression are prevalent among cancer patients and impact treatment outcomes.
Stress-related conditions correlate with negative cancer outcomes, such as progression and metastasis.
Animal Models: Stress in mice simulates negative cancer outcomes observed in human epidemiological studies.
Stress can influence neuroendocrine factors, reshaping local and systemic immune responses.
Stress and Brain-Gut Axis: Stress leads to microbial dysbiosis and inflammatory responses impacting cancer development.

Stress-Induced Factors: SAM and HPA axes involve catecholamines and glucocorticoids.
Catecholamines activate adrenergic receptors, leading to immune modulation.
Neurotransmitters like serotonin and acetylcholine play roles in stress adaptation and immune responses.

SAIMs can modulate the immune system's response to tumors.
Glucocorticoids: Can be either immunosuppressive or immunostimulatory, depending on various factors.
Catecholamines: Generally immunosuppressive, influencing T cell function and promoting tumor progression.
Neuroendocrine factors influence immune cell metabolism and function.

Immune Contexture: The presence of leukocyte subpopulations impacts cancer evolution and response to therapy.
Stress can modulate tumor immunosurveillance.
High stress levels are associated with impaired NK cell function and increased regulatory T cell levels.

SAIMs can induce systemic metabolic reprogramming, affecting immune responses.
Metabolic Reprogramming: Changes in energy supply and metabolite availability impact immune cells.
Stress often disrupts the brain-gut axis, leading to immune dysregulation.

Stress influences cancer immunosurveillance through complex interactions involving neuroendocrine factors, metabolism, and microbiota.
Understanding these interactions requires interdisciplinary research in neuroscience, immunology, microbiology, and oncology.
The potential for targeting neuroendocrine pathways and stress management as therapeutic strategies for cancer.

Research supported by various national and international institutions, including the Science and Technology Innovation Major Project and Natural Science Foundation of China.