The role of neuro-immune interactions in cancer-related fatigue: Biobehavioral risk factors and mechanisms

Abstract

Fatigue is a common and distressing symptom in both patients with cancer and cancer survivors. There is substantial variation in the severity and persistence of cancer-related fatigue that may be driven by individual differences in host factors, including characteristics that predate the cancer experience as well as responses to cancer and its treatment. This review examines biobehavioral risk factors linked to fatigue and the mechanisms through which they influence fatigue across the cancer continuum, with a focus on neuro-immune processes. Among psychosocial risk factors, childhood adversity is a strong and consistent predictor of cancer-related fatigue; other risk factors include history of depression, catastrophizing, lack of physical activity, and sleep disturbance, with compelling preliminary evidence for loneliness and trait anxiety. Among biologic systems, initial work suggests that alterations in immune, neuroendocrine, and neural processes are associated with fatigue. The identification of key risk factors and underlying mechanisms is critical for the development and deployment of targeted interventions to reduce the burden of fatigue in the growing population of cancer survivors. Given the multidimensional nature of fatigue, interventions that influence multiple systems may be most effective.

Keywords: biobehavioral; fatigue; inflammation; neuro-immune; psychosocial.

Figure 1

The figure highlights key pathways and factors that may influence CRF based on a biobehavioral model. In this model, fatigue is precipitated (or worsened) by the effects of cancer and its treatment on the brain, the neuroendocrine system, and the immune system. These lead to the production of proinflammatory cytokines from immune cells, which signal the brain to induce fatigue. Individual differences at each level of the model can modulate the severity and duration of this response. Predisposing factors are present before diagnosis and treatment and may increase vulnerability to CRF. potentially through effects on inflammatory processes as well as regulation of and sensitivity to those processes. Perpetuating factors include psychological/ behavioral and biologic responses to diagnosis and treatment that potentially can be targeted for intervention. ANS indicates autonomic nervous system: HPA axis, hypothalamic-pituitary-adrenal axis: SNPs. single-nucleotide polymorphisms.