Stress acts as a relevant and integral piece to our daily lives. Defined as a stimulus that precipitates a physiological reaction in the brain, stress functions to activate a response in the body that has historically served as a survival mechanism for the human population. Stress can be caused by daily responsibilities and routines or more traumatic events, such as development of an illness or hospitalization. Sustained levels of elevated stress responses causes profound alterations in proper functionality of immune system physiology, potentially leading to development and propagation of various chronic illnesses, including cancer.
The magnitude and duration of elevations in stress hormones affects immune cell trafficking and function, thereby affecting health outcomes. In order to further understand this concept, it is important to survey the types of immune system responses responsible for overall health and wellbeing.
Protective Immune System
First, the protective part of the immune system mechanistically functions to elicit immediate action in response to wounds, trauma, and/or infection. This involves many of the “fight or flight” hormones – such as epinephrine, norepinephrine, and cortisol. In terms of cancer, this piece is vital for appropriate monitoring of cell surveillance, especially in terms of cancer progression, invasion, and metastasis. With overactivity, the effects of this aspect of the immune system become more burdensome than beneficial. In fact, enhancement of carcinogenic properties due to overstimulation of these hormones is most notable in prostate, ovary, breast, and colon cancer cells. In addition, chronic stress has been shown to suppress the functionality of this part of the immune system, thereby negating appropriate activity and response to cancerous cells. Mice studies demonstrate chronic stress likely contributes to increased tumor burden and likelihood of new blood vessel growth and metastasis in the cancer environment. Human studies have further revealed that higher, sustained diurnal cortisol levels indicative of high stress showed significantly decreased and sluggish immune function.
Inflammatory Immune System
The second major response from the immune system occurs following a higher level of stress that leads to cellular production of inflammatory mediators, above what is naturally produced. A sustained period of stress-induced inflammatory mediator production creates an environment where cancer may begin, progress, and/or spread. This is evidenced by sites of chronic inflammation eventually developing into an associated cancer (ie: gastrointestinal autoimmune disease potentially leading to gastrointestinal cancer.) In addition, quality of life for a patient with a cancer diagnosis may be greatly impacted by the sustained level of inflammation, leading but not limited to fatigue, depression, and sleep disturbances. A human study demonstrated a greater negative affect or mood in post-surgical breast cancer patients was related to pro-inflammatory cell production and involvement favoring disease progression.
At certain times, it can be rather challenging to completely avoid or mitigate stress; however, it’s important to note the power of managing the response to the stress. It has become clear that psychological well-being and perceived quality of life significantly impacts survivorship amongst patients diagnosed with cancer. Many known techniques can indirectly modulate the stress responses as noted above; thereby increasing the effectiveness of immune function overall. Although specific studies detailing outcomes of emphasizing stress management techniques and modulation of physiology as it relates to cancer are not readily available, one can glean profound conclusions based on existing published material.
Effective techniques for managing the stress response:
- Mindfulness-based techniques
Mindfulness-based techniques requires bringing attention or an awareness to present emotions while withholding judgement. In other words, it involves becoming more aware of one’s emotional, mental, and physical experiences in the present moment without being influenced or becoming overwhelmed by them. This allows one to gain theoretical control over their perceived thoughts in a particular situation. Mindfulness-based techniques can be performed in conjunction with other activities such as guided-meditation, yoga, cognitive behavioral therapy, and guided imagery. A study evaluating the effects of yoga in patients with breast cancer showed an overall decrease in pro-inflammatory cells following a 3 month regimen. Another study demonstrated that the use of psychosocial interventions providing stress reduction and emotional support, including mindfulness meditation and yoga, in patients with stage I-III breast cancer increased the likelihood of maintained telomere length, indicative of positive prognosis. Lastly, a study researching the effects of mindfulness-based techniques, specifically cognitive behavioral therapy, confirmed a decrease in serum evening cortisol and increase in cells related to cancer immunosurveillance. Not to mention that mindfulness implementation also served to benefit quality of life, especially in terms of pain, insomnia, fatigue, and overall perceived outlook.
Spending time in nature provides quantifiable mental and physical benefits in relation to immune function and stress response. Recognized as a relaxation and stress-management technique, forest bathing or a leisurely trip through a forested area has proven to affect cellular activity as well as overall emotional health. More specifically, inhalation of vaporized oils naturally produced by trees, called phytoncides, has been shown to increase cellular immune activity and count – specifically natural killer cells which play a role in cytotoxicity and cancer cell death. Serum testing revealed this increased activity has been shown to last for up to 30 days post-exposure to nature. In addition, it has been shown that salivary levels of the main stress hormones, including cortisol, epinephrine, and adrenaline were reduced following time spent in nature. Randomized trials have demonstrated that images of nature lessened stress activity within the brain in conjunction with decreased perceived mental rumination of thoughts.
In conclusion, opportunity exists for altering one’s response to stress which in turn may affect quantifiable and qualitative aspects of cancer and quality of life. It is evident that introducing techniques to moderate the stress response have confirmed positive effects in activation of the immune system. This may play an impactful role in overall well-being within various stages of cancer care.
References and Resources
Antoni MH, Lutgendorf S, Blomberg B, Carver CS, Lechner S, Diaz A, Stagl J, Arevalo J, and Cole S. Cognitive-behavioral stress management reverses anxiety-related leukocyte transcriptional dynamics. Biological Psychiatry 2012;71: 366-373. [PubMed: 22088795].
Carlson LE, Beattie TL, Giese-Davis J, Faris P, Tamagawa R, Fick LJ, Degelman ES, Speca M. Mindfulness-based cancer recovery and supportive-expressive therapy maintain telomere length relative to controls in distressed breast cancer survivors. Cancer. 2015 Feb 1;121(3):476-84. doi: 10.1002/cncr.29063. Epub 2014 Nov 3. PMID: 25367403.
Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420: 860-867. [PubMed: 12490959].
Dhabhar FS, Saul AN, Holmes TH, et al. High anxiety is associated with higher chronic stress burden, lower protective immunity, and increased cancer progression. PLoS One. 2012;7: DOI: 10.1371/journal.pone.0033069.
Kiecolt-Glaser K, Bennett J, Andridge R, Peng J, Shapiro C, Malarkey W, Emery C, Layman R, Mrozek E, and Glaser R. Yoga’s impact on inflammation, mood, and fatigue in breast cancer survivors: a randomized controlled trial. Journal of Clinical Oncology. 2014:32 (10): 1040-1049. [PubMed: 24470004].
Li Q. Effect of forest bathing trips on human immune function. Environ Health Prev Med. 2010;15(1):9-17. doi:10.1007/s12199-008-0068-3
Saul AN, Oberyszyn TM, Daugherty C, et al. Chronic stress and susceptibility to skin cancer. J Nat Cancer Institute. 2005;97: 1760-1767.
Sephton SE, Dhabbar FS, Keuroghlian AS, et al. Depression, cortisol, and suppressed cell-mediated immunity in metastatic breast cancer. Brain Behav Immun. 2009;23: 1148-1155. [PubMed 19643176].
Wurtzen H, Dalton S, Elsass P, Sumbundu A, Steding-Jensen M, Larsen R, Andersen K, Flyger H, Pedersen A, and Johansen C. Mindfulness significantly reduces self-reported levels of anxiety and depression: results of a randomized controlled trial among 336 Danish women treated for stage I-III breast cancer. European Journal of Cancer. 2013;49: 1365-1373. [PubMed: 23265707].