Abstract 7565: Psychological distress, antidepressants, and sympathetic-immune profiles in cancer survivors.

Abstract Background: Psychological distress, including perceived stress, anxiety, and depression, can activate the sympathetic nervous system and increase norepinephrine (NE) and epinephrine (E). These catecholamines may impair anti-tumor immunity through β2-adrenergic effects on CD8+ T-cells and myeloid-derived suppressor cells (MDSCs). Antidepressants that alter NE reuptake may further modify sympathetic signaling and immune regulation in cancer survivors. Methods: This analysis included 152 cancer survivors who completed the Perceived Stress Scale (PSS), PROMIS Anxiety (PROMIS), and Center for Epidemiological Studies Depression (CES-D) surveys and reported clinical diagnosis of anxiety or depression and current antidepressant use. Plasma NE, E, 3,4-dihydroxyphenylglycol (3,4-DHPG), and dopamine (DA) were quantified by LC-MS/MS, and CD8+ T-cell and MDSC subsets were assessed by flow cytometry as percent cell-subset events over total cell type events. Antidepressant use was classified as none (N=120), selective serotonin reuptake inhibitor (SSRI, N=11), or serotonin-NE or NE-DA reuptake inhibitors (SNRI/NDRI, N=21); five clinically diagnosed individuals not taking antidepressants were excluded. Associations of distress measures, clinical diagnoses, and medication class with catecholamines and immune profiles were evaluated using ANCOVA adjusted for age, education, and smoking history, with reciprocal adjustment for PROMIS or CES-D in clinical diagnosis models. Results: Catecholamine levels were not associated with PSS, PROMIS, or CES-D. Higher perceived stress was associated with altered CD8+ T-cell distributions: naïve CD8+ T-cells were 30.7% higher in the highest vs lowest quartile (62.2 vs 47.6%, p=0.03), while memory CD8+ T-cells were 28.5% lower (36.6 vs 51.2%, p=0.01). Clinical anxiety (N=23) was not related to catecholamine levels, but clinical depression (N=24) was associated with higher NE (22.2%; 663.0 vs 542.2 pg/mL, p=0.01) and DA (41.8%, 20.5 vs 14.5 pg/mL, p=0.002). Neither diagnosis was associated with CD8+ T-cells or MDSCs. Antidepressant class showed expected physiologic patterns: SNRI/NDRI users had higher NE (37.7%; 485.3 vs 352.4, p=0.04), lower 3,4-DHPG (19.9%; 912.7 vs 1139.4 pg/mL, p=0.0004), and higher DA (64.5%, 16.1 vs 9.8 pg/mL, p=0.001) than SSRI users. PMN-MDSCs trended 32.2% higher (1.15 vs 0.87%, p=0.11) and M-MDSCs 54.8% higher (4.32 vs 2.79%, p=0.09) among SNRI/NDRI users vs SSRI users, consistent with increased adrenergic-linked immunosuppressive myeloid activity. Conclusion: Clinical depression was associated with higher sympathetic catecholamines, and NE-reuptake-inhibiting antidepressants produced expected catecholamine shifts. Corresponding increases in PMN-MDSC and M-MDSC among SNRI/NDRI users suggest adrenergic signaling may contribute to immunosuppressive myeloid abundance in cancer survivors. Citation Format: Ji E. Park, Andrew Ray, Rikki Cannioto, Kathryn Glaser, Han Yu, Karen Hulme, Susan LaValley, Orla Maguire, Hans Minderman, Krystin Mantione, Nicolas Schlecht, Shipra Gandhi, Elizabeth Bouchard, Elizabeth Repasky, Christine Ambrosone, Chi-Chen Hong. Psychological distress, antidepressants, and sympathetic-immune profiles in cancer survivors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7565.