The Stress-Induced T-helper 2 Shift Linked to Colon Cancer Growth: Data from a Novel Experimental Stress Model


The Stress-Induced T-helper 2 Shift Colon Cancer
The stress-induced t-helper2-shift – colon cancer

Update at BrainImmuneIn the October 2013 issue of Biochemical and Biophysical Research Communications, Ni Hou and colleagues from the Xi’an Jiaotong University School of Medicine, Xi’an, Shaanxi, China, demonstrated that a novel form of sound stress induced a T helper (Th)2 shift and that this is related to colon cancer progression in mice.

Colorectal cancer is the third most common cancer worldwide, and numerous epidemiological reports indicate a connection between stress and cancer.

For example, data related to a Finnish twin cohort study or the Chinese Cultural Revolution suggests a link between stressful life events and cancer.

Furthermore, fundamental and clinical studies demonstrate that psychological stress and other biobehavioral factors may contribute to cancer onset and progression. For instance, breast cancer, ovarian cancer, leukemia and prostate cancer have been linked to stress, stress hormones or sympathetic innervation.

T helper (Th)1 immunity is considered a major defense mechanism in immunosurveillance related to tumor development. A profound Th2 shift linked to a deficiency of IL-12, and overproduction of IL-10 and TGF-β seems to play an inappropriate immunosuppressive role, allowing increased tumor growth (Chouaib, S et al., Immunol. Today, 1997, 18:493).

Stress is often regarded as immunosuppressive. Evidence accumulated over the last 2-3 decades, however, indicates that acute, subacute or chronic stress might suppress cellular immunity but boost humoral immunity. This is mediated by a differential effect of stress hormones, the glucocorticoids and catecholamines, on T helper 1 (Th1)/Th2 cells and type 1/type 2 cytokine production. The principal peripheral stress hormones, glucocorticoids and catecholamines mediate the shift towards a T helper-2 (Th2) response by suppressing antigen presentation and Th1 production and by upregulating Th2 cytokine production.

In addition, both glucocorticoids and catecholamines upregulate the immunosuppressive IL-10 (IJ Elenkov & GP Chrousos, Trends Endocrinol Metab, 1999, 10:359), while stress may restrain the immunostimulatory effects of interleukin-12. Thus, stress-hormone-induced suppression of cellular immunity might contribute to increased growth of certain tumors.

Animal models have been often used to study these interactions.

In fact, two reports in Science magazine, using mice subjected to inescapable shock were perhaps the first to document a link between experimental stress and tumor growth (Sklar LS & Anisman H, Science, 1979, 205:513; Visintainer MA et al., Science. 1982, 216:437).

In the Biochemical and Biophysical Research Communications study, Ni Hou et al. report that mice exposed to a chronic scream sound stress (frequencies from 0.5 kHz to 4 kHz; 6 h daily for 2 weeks), when compared to control animals, had enlarged adrenal cortex zona fasciculata, and increased serum concentrations of norepinephrine (noradrenaline) and corticosterone.

These mice also had lower microarray intensities of serum TNF-α and IL-2 (Th1 cytokines), higher intensities of serum IL-4, IL-5, IL-6, IL-10, and IL-13 (Th2 cytokines), and decreased IFN-γ/IL-4 ratio in tumor infiltrated lymphocytes and tumor microenvironment.

All these neurohormonal-immune changes were associated with morphological alterations indicating colon cancer progression. These results may suggest that further studies investigating the impact of chronic stress on colon cancer progression are warranted.

Thus, this study indicates that chronic scream sound exposure in our experiment induced freezing behavior in the mice and decreased the bodyweight gain. The changes in the adrenal gland and serum corticosterone and norepinephrine levels also indicates that chronic exposure to scream sound led to a stress response and caused stress in Balb/c mice, and to some degree of The shift.

Source: Biochem Biophys Res Commun, 2013, 439:471-6. doi:10.1016/j.bbrc.2013.08.101. Epub 2013 Sep 10
Read more: Biochemical and Biophysical Research Communications


A 2017 study by Norimasa Kikuchi et al. conducted a large-scale prospective cohort study to confirm the association between perceived stress and colorectal cancer incidence. The authors identified 680 cases of colon cancer and 330 cases of rectal cancer during a maximum of 21-year follow-up of 61,563 Japanese men and women.

The authors found that perceived stress was significantly associated with the risk of rectal cancer, but not with the risk of colon cancer. The association between perceived stress and rectal cancer incidence remained consistent across three statistical models used by these investigators, suggesting that this association or link is significant. The authors concluded that studies on this topic are sparse and warrant further exploration.

Interestingly, a 2018 medical hypothesis by Qi Zhang et al. suggested that prenatal risk factors such as maternal stress and associated sleeping disorders influence offspring epigenetic make-up, and shape immune system and gut health contributing to an increased risk for early-onset colorectal cancer (EOCRC, as colorectal cancer diagnosed before the age of 50)

A 2019 A meta-analysis found a significant association between work stress and the risk of colorectal, lung, and esophagus cancers. A statistically significant effect of work stress on colorectal cancer risk was observed in North America but not significant in Europe.

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