Elsevier

The Lancet Oncology

Volume 5, Issue 10, October 2004, Pages 617-625
The Lancet Oncology

Review
Stress, depression, the immune system, and cancer

https://doi.org/10.1016/S1470-2045(04)01597-9Get rights and content

Summary

The links between the psychological and physiological features of cancer risk and progression have been studied through psychoneuroimmunology. The persistent activation of the hypothalamic-pituitary-adrenal (HPA) axis in the chronic stress response and in depression probably impairs the immune response and contributes to the development and progression of some types of cancer. Here, we overview the evidence that various cellular and molecular immunological factors are compromised in chronic stress and depression and discuss the clinical implications of these factors in the initiation and progression of cancer. The consecutive stages of the multistep immune reactions are either inhibited or enhanced as a result of previous or parallel stress experiences, depending on the type and intensity of the stressor and on the animal species, strain, sex, or age. In general, both stressors and depression are associated with the decreased cytotoxic T-cell and natural-killer-cell activities that affect processes such as immune surveillance of tumours, and with the events that modulate development and accumulation of somatic mutations and genomic instability. A better understanding of the bidirectional communication between the neuroendocrine and immune systems could contribute to new clinical and treatment strategies.

Section snippets

Physiological response to stress

Stressful experiences include physical stressors such as pathogens and toxins, and psychological stressors such as major life events, trauma, abuse, or factors related to the environment in the home, workplace, family, or neighbourhood. The ability to adjust or habituate to repeated stress is also determined by the way a person perceives a situation.6

The major neural pathways activated by stressors are the HPA axis and the sympathetic nervous system.1, 2, 3, 5, 7, 8, 9 Neurosensory signals are

Role of stress and depression

The effect of psychological factors on cancer depends very much on the type of tumour involved. Moreover, the validity of many of the data has been questioned because retrospective studies tend to show associations that are linked in the memory of individuals, and much information about real-life stressors could possibly be lost, whereas unliked phenomena are remembered less well. These observations, which are the core of psychosomatic medicine, have been rejected or ignored by many scientists

Effects on cancer

Cancer is a heterogeneous group of diseases with multiple causes, and immunological involvement varies across different cancers. Cancers induced by chemical carcinogens might be less affected by psychological, behavioural, and immunological factors than are those associated with a DNA tumour virus, retrovirus insertion near a cellular oncogene, or other viruses such as Epstein Barr virus, which is immunogenic. Suppression of cellular immunity is associated with a higher incidence of some types

Clinical implications

The determination of the role of stress in the onset and progression of cancer has faced many difficulties such as the stage of the disease and health behaviours. In addition to the direct effects of psychological states on physiological function, individuals who are stressed and depressed are more likely to have health habits that put them at great risk, including worse sleep, a greater propensity for alcohol and drug abuse, worse nutrition, and less exercise—health behaviours that have

Conclusion

Evidence mainly from animal models and human studies suggests that stress and depression result in an impairment of the immune response and might promote the initiation and progression of some types of cancer, mainly associated with a DNA tumour virus, retrovirus insertion near a cellular oncogene, and other viruses such as EBV. Through HPA activation, the mediators released during chronic stress suppress some non-specific and specific parts of the immune response, including NK-cell activity,

Search strategy and selection criteria

The authors accessed personal collections of reprints, scanned key journals, contacted colleagues, and searched databases such as Medline, PubMed, and OVID, between 1977 and 2003, using the keywords “cytokines and brain”, “cytokines and cancer”, “stress hormones”, “psychological stress and cancer”, “depression and cancer”, “psycho- neuroimmunology”. Only papers published in English were selected. To simplify the review, the authors arbitrarily chose the studies, in an attempt to review the

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