Psychological factors and immune–inflammatory mechanisms in cancer-related organ transplantation: Toward a multimodal integrative framework
Abstract
Cancer patients who undergo organ transplantation after oncologic treatment experience complex biological and psychological stressors that jointly influence immune recovery and graft function. Psychological distress—particularly anxiety and depression—activates neuroendocrine and autonomic pathways that modulate cytokine release, inflammation, and immune tolerance. Evidence from psycho-oncology and transplantation studies demonstrates that heightened distress and low resilience correlate with increased interleukin-6, tumour necrosis factor-α, and C-reactive protein levels, impaired cellular immunity, and delayed post-operative recovery. This review integrates current findings from psychoneuroimmunology, transplantation medicine, and behavioural oncology to elucidate how donor characteristics, perfusion parameters, and psychosocial factors interact to shape outcomes in cancer-related transplantation. Routine psychological assessment using validated instruments such as the Hospital Anxiety and Depression Scale (HADS), together with early interventions—cognitive-behavioural therapy, mindfulness-based stress reduction, and resilience training—may reduce inflammatory activity and improve recovery trajectories. Furthermore, emerging multimodal and machine-learning-assisted analytic approaches provide opportunities for personalised psychosocial care and risk stratification. Understanding these psych neuroimmune interactions supports the development of integrative, precision-based rehabilitation strategies within the scope of psycho-oncology.
Copyright (c) 2026 Guozhen Chen, Chenguang Ding, Haiping Liu, Wujun Xue
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
1. McDonald PG, O’Connell M, Lutgendorf SK. Psychoneuroimmunology and cancer: A decade of discovery, paradigm shifts, and methodological innovations. Brain, Behavior, and Immunity.2013; 30: S1–S9. doi: 10.1016/j.bbi.2013.01.003
2. Chang A, Sloan EK, Antoni MH, et al. Biobehavioral pathways and cancer progression: Insights for improving well-being and cancer outcomes. Integrative Cancer Therapies. 2022; 21: 15347354221096081. doi: 10.1177/15347354221096081
3. Polomeni A, Moreno E, Schulz-Kindermann F. Psychological morbidity and support. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies. 2018; 221–227. doi: 10.1007/978-3-030-02278-5
4. Segerstrom SC, Miller GE. Psychological stress and the human immune system: A meta-analytic study of 30 years of inquiry. Psychological Bulletin. 2004; 130(4): 601. doi: 10.1037/0033-2909.130.4.601
5. Kiecolt-Glaser JK, Glaser R. Depression and immune function: central pathways to morbidity and mortality. Journal of Psychosomatic Research. 2002; 53(4): 873–876. doi: 10.1016/S0022-3999(02)00309-4
6. Bezu L, Akçal Öksüz D, Bell M, et al. Perioperative immunosuppressive factors during cancer surgery: An updated review. Cancers. 2024; 16(13): 2304. doi: 10.3390/cancers16132304
7. Fox S, Lynch J, D’Alton P, et al. Psycho-oncology: A bibliometric review of the 100 most-cited articles. Healthcare. MDPI. 2021; 9(8): 1008. doi: 10.3390/healthcare9081008
8. Klapheke MM. Transplantation psychoneuroimmunology: Building hypotheses. Medical Hypotheses. 2000; 54(6): 969–978. doi: 10.1054/mehy.1999.0998
9. Swanson KJ, Bhattarai M, Parajuli S. Delayed graft function: current status and future directions. Current Opinion in Organ Transplantation. 2023; 28(1): 1–7. doi: 10.1097/MOT.0000000000001034
10. Yao Z, Kuang M, Li Z. Risk factors for delayed graft function in patients with kidney transplantation: A systematic review and meta-analysis. BMJ Open. 2025; 15(3): e087128. doi: 10.1136/bmjopen-2024-087128
11. Kelly D L, Syrjala K, Taylor M, et al. Biobehavioral research and hematopoietic stem cell transplantation: Expert review from the biobehavioral research special interest group of the american society for transplantation and cellular therapy. Transplantation and Cellular Therapy. 2021; 27(9): 747–757. doi: 10.1016/j.jtct.2021.06.007
12. McGregor BA, Syrjala KL, Dolan ED, et al. The effect of pre-transplant distress on immune reconstitution among adult autologous hematopoietic cell transplantation patients. Brain, Behavior, and Immunity. 2013; 30: S142–S148. doi: 10.1016/j.bbi.2012.07.020
13. Pulgar Á, Garrido S, Alcalá A, et al. Psychosocial predictors of immune response following bone marrow transplantation. Behavioral Medicine. 2012; 38(1): 12–18. doi: 10.1080/08964289.2011.647118
14. Hoodin F, Kalbfleisch KR, Thornton J, et al. Psychosocial influences on 305 adults’ survival after bone marrow transplantation: Depression, smoking, and behavioral self-regulation. Journal of Psychosomatic Research. 2004; 57(2): 145–154. doi: 10.1016/S0022-3999(03)00599-3
15. Dhabhar FS. Effects of stress on immune function: The good, the bad, and the beautiful. Immunologic Research. 2014; 58(2): 193–210. doi: 10.1007/s12026-014-8517-0
16. Padgett DA, Glaser R. How stress influences the immune response. Trends in Immunology. 2003; 24(8): 444–448. doi: 10.1016/S1471-4906(03)00173-X
17. Irwin MR, Cole SW. Reciprocal regulation of the neural and innate immune systems. Nature Reviews Immunology. 2011; 11(9): 625–632. doi: 10.1038/nri3042
18. Capuron L, Miller AH. Cytokines and psychopathology: Lessons from interferon-α. Biological Psychiatry. 2004; 56(11): 819–824. doi: 10.1016/j.biopsych.2004.02.009
19. Bower JE, Ganz PA, Irwin MR, et al. Inflammation and behavioral symptoms after breast cancer treatment: do fatigue, depression, and sleep disturbance share a common underlying mechanism? Journal of Clinical Oncology. 2011; 29(26): 3517–3522. doi: 10.1200/JCO.2011.36.1154
20. Miller A H, Haroon E, Raison CL, et al. Cytokine targets in the brain: Impact on neurotransmitters and neurocircuits. Depression and Anxiety. 2013; 30(4): 297–306. doi: 10.1002/da.22084
21. Tavakoli-Ardakani M, Beyraghi N, Mirjalili M, et al. Effect of pretransplant depression on neutrophil recovery following hematopoietic stem cell transplantation. Transplant Research and Risk Management. 2019; 1–9. doi: 10.2147/TRRM.S194011
22. Black DS, Slavich GM. Mindfulness meditation and the immune system: A systematic review of randomized controlled trials. Annals of the New York Academy of Sciences. 2016; 1373(1): 13–24. doi: 10.1111/nyas.12998
23. Mirmahmoodi M, Mangalian P, Ahmadi A, et al. The effect of mindfulness-based stress reduction group counseling on psychological and inflammatory responses of the women with breast cancer. Integrative Cancer Therapies. 2020; 19: 1534735420946819. doi: 10.1177/1534735420946819
24. Antoni MH, Lehman JM, Kilbourn KM, et al. Cognitive-behavioral stress management intervention decreases the prevalence of depression and enhances benefit finding among women under treatment for early-stage breast cancer. Health Psychology. 2001; 20(1): 20. doi: 10.1037/0278-6133.20.1.20
25. Shields GS, Spahr CM, Slavich GM. Psychosocial interventions and immune system function: A systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry. 2020; 77(10): 1031–1043. doi: 10.1001/jamapsychiatry.2020.0431
26. Dew MA, Rosenberger EM, Myaskovsky L, et al. Depression and anxiety as risk factors for morbidity and mortality after organ transplantation: A systematic review and meta-analysis. Transplantation. 2016; 100(5): 988–1003. doi: 10.1097/TP.0000000000000901
27. Fukunishi I, Sugawara Y, Takayama T, et al. Association between pretransplant psychological assessments and posttransplant psychiatric disorders in living-related transplantation. Psychosomatics. 2002; 43(1): 49–54. doi: 10.1176/appi.psy.43.1.49
28. Nance DM, Sanders VM. Autonomic innervation and regulation of the immune system (1987–2007). Brain, Behavior, and Immunity. 2007; 21(6): 736-745. doi: 10.1016/j.bbi.2007.03.008
29. Kim Y, Lin J, Epel ES, et al. A lens on caregiver stress in cancer: longitudinal investigation of cancer-related stress and telomere length among family caregivers of adult patients with cancer. Psychosomatic Medicine. 2023; 85(6): 527–534.
30. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatrica Scandinavica. 1983; 67(6): 361–370. doi: 10.1111/j.1600-0447.1983.tb09716.x
31. Donovan KA, Grassi L, McGinty HL, Jacobsen PB. Validation of the distress thermometer worldwide: state of the science. Psychooncology. 2014; 23(3): 241–250. doi: 10.1002/pon.3430
32. Carlson LE, Speca M, Faris P, et al. One year pre–post intervention follow-up of psychological, immune, endocrine and blood pressure outcomes of mindfulness-based stress reduction (MBSR) in breast and prostate cancer outpatients. Brain, Behavior, and Immunity. 2007; 21(8): 1038–1049. doi: 10.1016/j.bbi.2007.04.002
33. Jen KY, Albahra S, Yen F, et al. Automated en masse machine-learning model generation shows comparable performance as classic regression models for predicting delayed graft function in renal allografts. Transplantation. 2021; 105(12): 2646–2654. doi: 10.1097/TP.0000000000003640
34. Grassi L, Caruso R, Sabato S, et al. Psychosocial screening and assessment in oncology and palliative care settings. Frontiers in Psychology. 2015; 5: 1485. doi: 10.3389/fpsyg.2014.01485
35. Breitbart W, Butow P, Jacobsen P, et al. Psycho-oncology. Oxford University Press; 2021.
36. Rodrigue JR, Mandelbrot DA, Pavlakis M. A psychological intervention to improve quality of life and reduce psychological distress in adults awaiting kidney transplantation. Nephrology Dialysis Transplantation. 2011; 26(2): 709–715. doi: 10.1093/ndt/gfq382
37. Lattie EG, Adkins EC, Winquist N, et al. Digital mental health interventions for depression, anxiety, and enhancement of psychological well-being among college students: systematic review. Journal of Medical Internet Research. 2019; 21(7): e12869. doi: 10.2196/12869
38. Lengacher C A, Johnson‐Mallard V, Post‐White J, et al. Randomized controlled trial of mindfulness‐based stress reduction (MBSR) for survivors of breast cancer. Psycho‐Oncology: Journal of the Psychological, Social and Behavioral Dimensions of Cancer. 2009; 18(12): 1261-–1272. doi: 10.1002/pon.1529
39. Loprinzi CE, Prasad K, Schroeder DR, et al. Stress Management and Resilience Training (SMART) program to decrease stress and enhance resilience among breast cancer survivors: A pilot randomized clinical trial. Clinical Breast Cancer. 2011; 11(6): 364–368. doi: 10.1016/j.clbc.2011.06.008.
40. Chida Y, Steptoe A. Positive psychological well-being and mortality: A quantitative review of prospective observational studies. Biopsychosocial Science and Medicine. 2008; 70(7): 741–756. doi: 10.1097/PSY.0b013e31818105ba
41. Sharp J, Wild MR, Gumley AI, et al. A cognitive behavioral group approach to enhance adherence to hemodialysis fluid restrictions: A randomized controlled trial. American Journal of Kidney Diseases. 2005; 45(6): 1046–1057. doi: 10.1053/j.ajkd.2005.02.032
42. DiMartini AF, Crone C, Rosenberger EM, et al. Psychiatric aspects of organ transplantation Focus. 2013; 11(4): 460–470. doi: 10.1176/appi.focus.11.4.460
43. Salemi MH, Foroozandeh E, Ashkzari MK. Applications, challenges, and future perspectives of artificial intelligence in psychopharmacology, psychological disorders and physiological psychology: A comprehensive review. Journal of Pharmacy and Bioallied Sciences. 2025; 17(Suppl 1): S229–S233. doi: 10.4103/jpbs.jpbs_1765_24
44. Stilley CS, DiMartini AF, de Vera ME, et al. Individual and environmental correlates and predictors of early adherence and outcomes after liver transplantation. Progress in Transplantation. 2010; 20(1): 58–66. doi: 10.1177/152692481002000110
45. Andersen BL, DeRubeis RJ, Berman BS, et al. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. Journal of Clinical Oncology. 2014; 32(15): 1605–1619. doi: 10.1200/JCO.2013.52.4611
