Stress reduces ICI drugs efficacy, Non-selective pan beta blockers can reduce this effect

[Olga]

Deb brought to our attention two articles that explain the aspect of stress and ICI drugs efficacy interaction and how the wide range of stressors have the same action - they suppress the immune system via norepinephrine release and impede the ICI drugs treatment that relies on immune cells availability, and what can be done about it.

1. In new preclinical research published online ahead of print in Cancer Research, a journal of the American Association for Cancer Research, a Roswell Park team led by Elizabeth Repasky, PhD, reports their important finding that beta-2 (β2) adrenergic receptors, molecules present in the cells of humans and other mammals, control the functionality of key immune cells. In response to stressors, these receptors turn on the “flight or fight” response. They generate more of the stress hormone norepinephrine, buffering normal cells from some damaging effects but also impeding the immune system’s ability to fight cancer.
Beta Blockers May Hold Key to Unleashing Potential of Checkpoint Inhibitors, Roswell Park Team Shows
https://www.roswellpark.org/media/news/ ... -park-team

2. The data raise the possibility that reducing stress signaling, particularly through the beta-2 adrenergic signaling pathway, can improve the efficacy of immune-based therapies for melanoma and perhaps other cancers as well, he said: "These results indicate that beta blockers and immunotherapy may synergize to enhance immune cell activity to a higher degree than either approach alone."
Beta Blockers May Enhance Immunotherapy Response in Advanced Melanoma
https://www.medpagetoday.com/reading-ro ... rapy/72430


So the lesson for us to take from this is:
1.The diff. types of stress (such as fear and anxiety, heat, cold, pain, depression and even attack by cancer cells) can reduce the efficacy of the ICI drugs. Try to reduce the stress by all means avail.
2. Non-selective pan beta blockers (such as propranolol) reduce the effects of binding of stress hormones (such as epinephrine and norepinephrine) and may improve anti-tumor immunity.
There are studies underway that look into what type of immune cells are suppressed by the stress hormones and how Beta Blockers work - if there is any direct anti-cancer or only hormonal immune modulating effect.