TNF and major depressive disorder: Research should consider other systemic biomarkers (eg, C-reactive protein, TNF-α, IL-1β, IL-6, and HPA axis dysregulation) as well as factors of the tumor microenvironment that may explain poor tumor response to treatment in patients with depressive symptoms.48,49 Given the strong associations of depression with neuroendocrine and immune changes, it is also reasonable to posit that depression may alter tumor response to treatment and cancer progression via peripheral cellular and molecular psychoneuroimmune changes.