Table 1_Depression and shortened survival in patients with cancer: a neuroimmune framework for bidirectional pathogenesis and therapeutic interception.docx

While emerging evidence suggests that depression reshapes both systemic and tumor-localized immunity via β-adrenergic and glucocorticoid signaling, the broader integrative pathways remain to be fully defined. To address this gap, this review synthesizes evidence from clinical, epidemiological, and translational studies to present a unifying systems-level framework: depression influences cancer outcomes through the coordinated dysregulation of the autonomic nervous system (ANS), hypothalamic-pituitary-adrenal (HPA) axis, and neuroimmune network.

Collectively, this triad fosters a pro-tumorigenic microenvironment. Unlike simpler linear models, this framework emphasizes the coupled, self-reinforcing interactions among these three systems. Specifically, sympathetic overdrive combined with vagal withdrawal amplifies the HPA output, peripheral inflammation sustains central dysregulation, and brain-derived neurotrophic factor (BDNF) dysfunction impairs neuroendocrine feedback.