Immunotherapy is a form of cancer treatment that stimulates and uses the body’s own immune system to fight cancer. Coffee, one of the most popular drinks across the world, has the potential to enhance anti-cancer immunity and complement various emerging pharmacological immunotherapy approaches. Coffee boosts anti-cancer immunity and complements immunotherapy by reactivating the immune system near the growing tumor, reducing new blood vessel formation and preventing the tumor from going into repair mode when damaged by cancer treatments.
Coffee is one of the most popular drinks in the United States and across the globe. A key component of coffee is the psychostimulant caffeine, that is also a significant component in caffeinated beverages, sodas, energy booster and other health drinks. Besides caffeine, coffee also has several other phytochemical components with anti-inflammatory and antioxidant properties. There are over 15,000 studies that have examined the health impact of drinking coffee and overall found it to be more healthful than harmful, when not used in excess.
Coffee has been shown to have numerous health benefits such as reducing cavities, boosting athletic performance, improving moods, and reducing headaches. Effects of coffee have also been shown to reduce the risk of various chronic and serious diseases such as type 2 diabetes, colon cancer, liver cancer, gallstones, cirrhosis of liver and Parkinson’s Disease. (Hong et al, Nutrients, 2020; Contaldo et al, Curr Opin Clin Nutr Metab Care, 2019; Kolb H et al, Nutrients, 2020)
In this blog, we will examine the ways in which coffee can enhance anti-cancer immunity and complement the various emerging pharmacological immunotherapy approaches. We will briefly describe how cancer co-opts the immune system to facilitate its own growth and survival and also provide a summary on the emergence of the new focus on using our own immune system to tackle and control cancer through the advances in various immunotherapy approaches, in order to highlight the complimentary effects of coffee.
Cancer Immunology 101
As is well known, cancer is a condition that is caused by the uncontrolled growth and spread of some cells in our body that have become abnormal and gone haywire. There are many causes of cancer that vary from having genetic susceptibility and familial risk factors, to lifestyle and environmental causes. Aging, obesity and other pro-inflammatory triggers and conditions also increase the risk of cancer.
Our bodies are equipped with our personal defense mechanism that is the immune system. It comprises many different cell types including macrophages, T cells, B cells, dendritic cells, natural killer cells, neutrophils and others that focus on protecting the body against infections and injury. The immune system in a healthy person has active surveillance to identify anything that is foreign, such as microbial bacteria and viruses, or damaged, due to injury or due to some cells within our body that have become cancerous, and wipe them out. We all have been vaccinated as children for various infections such as polio, smallpox, measles, mumps and others to prime the immune system to recognize these known harmful microbes and be ready to fight against them when needed.
The immune system is very finely balanced. When overstimulated, it can attack ‘self’ and result in autoimmune disorders such as rheumatoid arthritis, multiple sclerosis and others. When the immune surveillance is dampened, it results in diseases such as cancer and other severe infectious diseases. The health of the immune system is impacted by our high stress lifestyles, our unhealthy diets, along with the natural aging process that reduces the fighting capabilities of the immune system.
Thus cancer cells can grow and thrive when they escape the immune surveillance. In addition, the cancer co-opts the immune system to not only protect it, but utilizes the immune machinery to facilitate progression of the disease through its robust growth and spread through the body. Cancer cells also have the ability to dampen the immune surveillance in its vicinity (microenvironment) and they thrive in an immunosuppressed environment.
Based on extensive scientific research and having understood the critical role of the immune system in supporting the cancer, there is renewed focus on different pharmacological approaches to stimulate and use the body’s own immune system to fight cancer. (Waldman AD et al, Nature Reviews Immunology, 2020) This form of cancer treatment that uses the body’s immune system to treat cancer is called immunotherapy. There are various immunotherapy approaches aimed at reducing the immunosuppression in the tumor microenvironment and enhancing the immune surveillance and activation of the immune cells. These include:
- Treating with immune mediators (cytokines) to activate the immune cells to attack the cancer.
- Inhibiting the inherent signals (checkpoint inhibitors) that are present to prevent the immune cells from attacking self, that have been co-opted by the cancer to prevent being recognized as abnormal and be destroyed.
- Using a patient’s own immune cells that have been extracted from their bodies and prepared externally to recognize and attack the cancer cells in an approach called adoptive cell therapy. CAR T (Chimeric antigen receptor T cells) has shown success in treating B cell malignancies.
- Cancer vaccines is another approach that is being investigated.
Ways in which Cancer Cells Avoid Immune Recognition
- The abnormal cancer cells create a microenvironment around themselves that is immunosuppressive and inhibits the activation and function of the immune cells.
- As the cancer grows, the abnormal cells learn to survive on low oxygen. This is a condition called hypoxia. Hypoxia in cancer cells triggers significant changes that further enhance survival. Hypoxia causes the excessive production of mediators that will increase blood supply to the cancer thus providing more nutrients, and also produces other mediators such as adenosine, that contribute to creating the immune suppression in its vicinity.
- Cancer cells also increase production of direct blockers to activation signals in immune cells (immune checkpoints) that prevent the immune cells from destroying the abnormal cancer cells.
How does Coffee Help with Boosting Anti-cancer Immunity?
Mentioned below are some of the ways in which coffee can enhance anti-cancer immunity.
Coffee reactivates the immune system near the growing tumor
The hypoxia environment created in cancer due to deprivation of oxygen limits the availability of energy sources and causes the accumulation of an energy intermediate called adenosine to accumulate externally in the cancer microenvironment. Adenosine helps in cellular energy transfer by forming the energy molecule ATP. It is also a signaling mediator and functions as an inhibitory neurotransmitter in the brain.
Adenosine binds to Adenosine receptors that have different effects on different cell types. Adenosine inhibits the activation of T-cells, B-cells, macrophages and dendritic cells but can activate the regulatory subset of T-cells, creating an immunosuppressive environment around the tumor.
Caffeine present in coffee also binds to the same receptors as adenosine and competes with it, thus antagonizing the adenosine action. In this manner, caffeine can interfere with and prevent adenosine from inhibiting the immune cells needed to recognize and clear out the abnormal tumor cell. (Merighi S et al, Mol. Pharmacol, 2007; Tej GNVC et al, Int. Immunopharmacol., 2019; Jacobson KA et al, Br. J Pharmacol, 2020)
Coffee reduces new blood vessel formation
Adenosine present in the tumor microenvironment increases the production of mediators such as interleukin 8 (IL8) and vascular endothelial growth factor (VEGF) that promote the formation of new blood vessels in a process called angiogenesis. This benefits the cancer cells to grab more of the nutrient supply for their growth and survival.
Coffee, by interfering with and antagonising adenosine action, can prevent this action of the tumor angiogenesis. (Gullanki Naga Venkata Charan Tej , Biomed Pharmacother., 2018)
Coffee prevents the tumor from going into repair mode when damaged by cancer treatments like chemotherapy and radiation therapy
Cancer treatments like chemotherapy and radiation therapy mediate their action through causing excessive DNA damage to the cancer cells, thereby causing the cells to die. The death of cancer cells can also activate the immune system that is needed to clear the dead cells. Cancer cells re-engineer themselves for survival and in the event of damage, upregulate the repair machinery through increasing the production of repair genes such as ATM and ATR.
Caffeine can inhibit ATM and ATR proteins and prevent repair of cancer DNA damage, thus making the cancer cell more vulnerable to being killed by other cancer treatments. (Li N et al., Biomed Res Int., 2018) By inhibiting the cellular repair machinery in cancer cells, caffeine helps with complementing the effects of chemotherapy and radiation therapy also, along with its actions on reducing the immune suppression in the tumor microenvironment.
Numerous beneficial effects of coffee have been highlighted based on scientific research. There is an emergence of focus on different pharmacological immunotherapy approaches, using our own immune defense to fight cancer, and the understanding of why the immune system is suppressed and unable to recognize the abnormal cancer cells in the body. This has propelled a search for natural and safe adjuvants that can reduce the immune resistance and boost the immune surveillance. The immune modulating effects of coffee, through antagonizing adenosine in the tumor microenvironment and thus reducing the immune suppression, can benefit and complement immunotherapy for controlling the cancer. However, despite the potential benefits of coffee in boosting anti-cancer immunity and complementing immunotherapy, excessive dosing of caffeine can be lethal. Coffee is a psychostimulant and should be taken in controlled and moderate amounts to harness its beneficial effects.
Cancer patients often have to deal with different chemotherapy side effects which affect their quality of life and look out for alternative therapies for cancer.Taking the right nutrition and supplements based on scientific considerations (avoiding guesswork and random selection) is the best natural remedy for cancer and treatment related side-effects.