Stress and cancer: The mechanisms of immune dysregulation and management

Abstract

Advances in the understanding of psychoneuroimmunology in the past decade have emphasized the notion that stress and cancer are interlinked closely. Durable chronic stress accelerated tumorigenesis and progression, which is unfavorable for clinical outcomes of cancer patients. Available evidence has provided unprecedented knowledge about the role and mechanisms of chronic stress in carcinogenesis, the most well-known one is dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). With abnormal activation of neuroendocrine system, stress-related hormones contribute to increased oncogenes expression, exacerbated chronic inflammation and impaired immunologic function. In addition, accumulating studies have demonstrated that diverse stress interventions including pharmacological approaches, physical exercises and psychological relaxation have been administered to assist in mental disorders reduction and life quality improvement in cancer patients. In this review, we systematically summarize the connection and mechanisms in the stress-immune-cancer axis identified by animal and clinical studies, as well as conclude the effectiveness and deficiencies of existing stress management strategies.

Inter- and transgenerational heritability of preconception chronic stress or alcohol exposure: Translational outcomes in brain and behavior

“…While to-date no published studies have investigated cross-generational ethanol exposure and cancer risk in animal models (though our laboratories are currently undertaking such a study), animal models have been suggested as a useful strategy for investigating alcohol effects on cellular immunity for decades ( Chirigos and Schultz, 1979 ). Preclinical studies within generations have found that both alcohol and chronic stress suppress the immune system in a way that is conducive to the development of tumors ( Chirigos and Schultz, 1979 ; Eckerling et al, 2021 ; Liu et al, 2022 ). However, a consensus on the extent of the effects of alcohol on development of cancerous tissue has not been reached because of variation in the methods used to induce cancers in animals ( Ratna and Mandrekar, 2017 ).…”

“…However, a consensus on the extent of the effects of alcohol on development of cancerous tissue has not been reached because of variation in the methods used to induce cancers in animals ( Ratna and Mandrekar, 2017 ). Preclinical evidence has also linked chronic stress to immune alterations that promote cancer development and metastasis, specifically through enhanced glucocorticoid, epinephrine, and norepinephrine signaling (for reviews, see: Cui et al (2021) ; Liu et al (2022) ; Dai et al (2020) ). However, this has primarily been studied in the context of existing tumor progression and treatment outcomes, and so it is currently unclear whether chronic stress alone increases cancer risk.…”

The cell stress and immunity cycle in cancer: Toward next generation of cancer immunotherapy

“…Conventional anticancer therapies like chemotherapy, radiotherapy, surgery, and molecularly targeted therapies have all strived to correct this dysregulation of the stress‐immunity cycle by killing cancer cells and reduce tumor burden 8–10 . Unfortunately, over the last decades, these conventional anticancer therapies have achieved limited success in meaningfully prolonging the survival of patients.…”

“…7 Conventional anticancer therapies like chemotherapy, radiotherapy, surgery, and molecularly targeted therapies have all strived to correct this dysregulation of the stress-immunity cycle by killing cancer cells and reduce tumor burden. [8][9][10] Unfortunately, over the last decades, these conventional anticancer therapies have achieved limited success in meaningfully prolonging the survival of patients. This is due to both primary and acquired resistance of cancer cells against these therapies as well as their inability to properly reactivate our immune system against (residual) cancer cells.…”

Association between Environmental Temperature and Survival in Gastroesophageal Cancers: A Population Based Study

“…Acute and chronic stressors are well-established modulators of the tumor microenvironment and significantly promote cancer invasion and progression through cascades of signaling pathways and adaptive immune responses [ 17 ]. Chronic cold stress has been found to prompt genetic and pre-genetic alterations and immunosuppressive responses, creating a pro-tumorigenic microenvironment [ 18 , 19 ].…”