Stress and Cancer from an Integrative Psychoneuroimmunology Perspective: Neurobiological Mechanisms and Clinical Implications.

Growing evidence from preclinical and clinical studies suggests that psychosocial factors, including stress, influence cancer incidence, progression, and survival. From a psychoneuroimmunology perspective, this integrative review synthesizes the neurobiological mechanisms underlying stress-cancer interactions, together with the epidemiological evidence supporting this relationship and its methodological limitations. Chronic stress impairs tumor immunosurveillance by CD8⁺ T cells and natural killer cells through dysregulation of the hypothalamic-pituitary-adrenal axis and sympathetic activation, and promotes angiogenesis and immunosuppression within the tumor microenvironment via β₂-adrenergic receptor signaling downstream of catecholamine release. Chronic exposure to catecholamines and cortisol has also been linked to cellular senescence and a senescence-associated secretory phenotype, raising the possibility that psychological stress contributes to accelerated biological aging in patients with cancer. In addition, individual genetic variability in adrenergic and glucocorticoid receptor signaling, counter-regulatory parasympathetic (vagal) anti-inflammatory pathways, and direct tumor innervation further modulate the magnitude and direction of stress effects on tumor biology. Chronic stress may also promote cancer risk indirectly through health behaviors such as smoking and physical inactivity, mediated by dopaminergic and cytokine-related neurobiological pathways. Together, these multilayered, bidirectional neuro-endocrine-immune mechanisms support viewing distress not merely as a source of psychological discomfort but as a biologically consequential factor in cancer care.