Body Terrain and the Tumor Microenvironment

In addition to malignant cells, the TME contains these types of cells:

• Immune system
• Tumor blood vessels
• Lymphatics
• Fibroblasts (cells in connective tissue that produce collagen and other fibers, usually to help wounds heal)
• Pericytes (cells in linings of blood vessels that help with blood vessel formation)
• Adipocytes (fat storage cells)

All the malignant and nonmalignant cells in the TME communicate with each other through a network of biochemical mediators: cytokines, chemokines and growth factors, as well as enzymes that promote inflammation and remodel the tissue matrix.

Considering the tumor microenvironment in an integrative oncology plan is important for these reasons:

• The cells in the TME play a role in cancer’s development, spread and response to treatment.
• Treatments that target the nonmalignant cells or the biochemical communication mediators in the TME may complement treatments that remove or kill cancer cells. An example of this is using anti-angiogenic treatments such as Avastin or Sutent to block the tumor from creating its blood supply.
• Complementary integrative approaches—such as diet, physical activity, natural products and stress management—may modify the terrain and sometimes specifically the TME, making the body less hospitable to cancer. These approaches may be important contributors in reducing risks of cancer, improving response to conventional treatments, improving quality of life during treatment, and maintaining remission.

Many weeds survive better in poor soil, while the plants we want to grow thrive in healthy soil. By building a healthy soil or inner terrain, a cancerous "weed" in your body is denied the environment that allows it to thrive. You also simultaneously promote health and wellness throughout your body.

Chemotherapy, radiation therapy and surgery are focused on killing or removing the cancer weed. Gardeners know that a pesticide or weed killer won’t work if you’ve mischaracterized the weed and used the wrong pesticide, or if you used a pesticide that the weed was resistant to. Successful gardeners know that if the soil is healthy, there’s less need to use pesticides and chemical fertilizers, because the soil’s healthy balance of microorganisms and biochemistry favors the growth of plants and deters weeds from taking hold.

Our body’s relationship with cancer is not too different. No matter how powerful our treatments are at killing the cancer (the weed), they will not succeed as long as the body provides the food and fodder for cancer to do what it does best: grow, circumvent programmed cell death, and spread.

Your integrative cancer care plan should include meaningful instruction and support in adopting or reinstating healthy lifestyle practices—the 7 Healing Practices. These practices foster a terrain conducive to health and less hospitable to cancer, with these potential benefits:

• Alter the tumor microenvironment
• Engage you meaningfully in your care
• Improve your quality of life on many levels

David Servan-Schreiber explains that “in patients who already have cancer, there is a ‘dose effect’ relationship between regular application of practices that improve lifestyles and the degree of protection from the disease. The more involved patients are in changing their terrain, the greater the benefits.”¹¹

Simple practices and habits, such as developing a practice of gratitude—consciously focusing on blessings—”may have emotional and interpersonal benefits”¹² that then impact physical and psychological/spiritual well-being.

Some additional healthy habits are deeply influential on your terrain:

• Maintaining a healthy weight
• Minimizing alcohol consumption
• Quitting smoking
• Keeping yourself hydrated

Excess body weight, alcohol and smoking foster terrain imbalances such as inflammation, hyperglycemia and insulin resistance, excess blood coagulation and reduced immunity.

We recognize that it is sometimes not easy to get rid of the extra weight, stop smoking, and drink alcohol moderately or not at all, but your terrain will love you for it and make it harder for cancer to grow or return. Support is available; see our Creating Healthy Habits page to get started.

Drinking an adequate amount of water and other non-alcoholic, unsweetened and non-caffeinated beverages every day may be easier to achieve. Nothing is more basically vital to life than being well-hydrated. Every cell and every function in your body depends on a healthy supply of water. See Dehydration and Hydration for specific information.

They explain that through these strategies we train our cells to retain their optimal resistance and effectiveness over cancer while also creating an environment that is less hospitable to cancer growth. First, the authors describe how cancer develops. Although cancer is characterized as a disease of genetic mutations, most of them don’t start with inherited gene mutations. Rather, the mutations are a result of mutated gene expression that develops over time.

“Cancer promoter genes are turned on, while cell repair and cancer-suppressor genes are switched off. This aberrant gene expression changes cell behavior, causing cells to divide too quickly, to spread into the surrounding tissue and to make proteins that call in new blood vessels. These changes, in turn, sustain the aberrant cells while maintaining a tissue environment that supports their continued growth. . . ultimately forming a cancerous tumor, or in the case of cancers of the blood, they circulate in malignant cell clusters. . . . Our lifestyle actually sends molecular messages to cell membranes that are then translated inside the cell and delivered to its very core, the nucleus, the home of DNA. There, these molecular signals interact with the DNA and become genetic switches that turn genes on and off. The on-and-off pattern determines the behavior of the cell and will ultimately move the cell toward improved function and health, or toward deviant behavior and disease.”¹³

In his book, Life over Cancer, Dr. Keith Block devotes an entire section on boosting your biology through using the healing power of terrain. “Your internal biochemistry can either nourish cancer cells or send them into molecular oblivion.”¹⁴ Block goes on to explain that the biochemical terrain is your body’s internal chemical environment, and it plays a vital role in “determining whether a tumor will regain its foothold after treatment, metastasizing to distant sites, or whether it will stay where it is without posing any threat. The internal biochemistry influences the microenvironment immediately surrounding the cancer cells. An inhospitable environment impacts the disease.”¹⁵ Similar to Alschuler and Gazella’s pathways, Block writes that addressing six “defining features” of your biochemical terrain is necessary. Cancer thrives on each of these when out of balance:

Eating well affects many of the factors defining one’s terrain. Dr. Keith Block reviews "terrain offenders" in his book Life Over Cancer. Some dietary offenders:⁴⁵

• Oxidation is increased by consuming alcohol, unhealthy fats, high levels of dietary iron, and eating more calories than you burn.
• Inflammation is increased by alcohol consumption, unhealthy dietary fats and carbohydrates, and unhealthy cooking methods.
• Immune surveillance is hampered by alcohol consumption, poor nutrition, unhealthy dietary fats, dairy foods, and iron-rich foods.
• Glycemia is tipped toward elevated blood sugar by eating too much, especially high glycemic-index foods and inflammation-producing foods, and by eating infrequent large meals.
• Stress biochemistry is thrown off balance by caffeine, alcohol, a low-carbohydrate and high-fat or high-protein diet, eating a high ratio of omega-6 to omega-3 fats, and overeating.

Oxidation is a good example of how eating habits and terrain are related. Oxidation creates free radicals that disable tumor-suppressor genes and/or activate tumor promoting genes (oncogenes). Oxidative stress can raise the malignant capabilities of a tumor.⁴⁶

Some foods are a source of oxidation, including too much fat, and especially saturated fats. Eating saturated fat, monounsaturated fat and animal fat is modestly associated with breast cancer risk and mortality,⁴⁷ and a small study found that women with breast cancer who ate higher levels of dietary fat had more damaged DNA in their tumors compared to women on a low-fat regimen.⁴⁸

Favor eating foods high in antioxidants:

• Colorful fruits and vegetables
• Barley, millet and oats
• Wild-caught salmon
• Legumes, especially soy, pinto, black, broad, kidney and small red beans
• Nuts and nut oils as well as extra virgin olive oil
• Tea
• Spices: oregano, dill, garlic, ginger, rosemary, cloves, sage, cumin, paprika

Alcohol consumption, another source of oxidative stress, is also associated with a higher risk of breast cancer.⁴⁹

The ketogenic diet is being studied as a possible means to affect cancer’s ability to co-opt the TME to support its altered energy metabolism. See our Ketogenic Diet summary.

For more information about eating well to support a healthy biochemical terrain, see our Eating Well summary.

Moving more is another powerful means of modifying your terrain to reduce the factors that nourish cancers, probably the reason it is included in every protocol we have investigated. For instance, being sedentary is associated with lower natural killer (NK) cell activity and impaired T cell function, both of which are necessary in finding and killing cancer cells (immune surveillance). Regular moderate activity such as walking, running and other exercises including resistance training can counter age-related decline in helper T cells and boost the number of NK cells in elderly men.⁵⁰ and in breast cancer survivors.⁵¹

Dr. Keith Block warns not to overdo exercise or abruptly change your exercise patterns, as this can actually depress the immune system. He advises to build up gradually to a healthy fitness level, be consistent and include yoga or qigong.

For more information, see our Moving More summary.

The biochemical alterations of chronic, unmanaged stress have widespread effects on terrain. As Dr. Block writes, “With your stress machinery stuck on high, continued exposure to stress hormones can severely damage your body and disturb your vital reserves of nutrients, enzymes, hormones, antibodies and immune cells, all of which are essential to your recovery.”⁵²

Effects of chronically elevated stress hormones:

• Increased blood glucose, insulin resistance and blood clotting factors
• Suppressed immune system
• Increased biochemicals that help tumors grow and spread.

High levels of stress hormones are associated with faster cancer progression, quicker relapse, reduced NK cell function and shorter survival.

For more information see our Managing Stress summary.

Sleep and stress are closely linked. Cancer incidence, progression and mortality are linked to stress and disruption of the circadian (daily) rest and activity cycle. Hormone levels, especially cortisol and melatonin, rise and fall with sleep and wakefulness. When these normal cycles are disrupted, the terrain is more hospitable toward cancer:

• Abnormally elevated cortisol caused by disrupted sleep pushes several cancer processes forward, especially metastasis.
• Melatonin, the “sleep hormone”, rises at night, but is either depressed or suppressed with disrupted sleep. Melatonin is instrumental in eliminating cancer cells and reducing the side effects of chemotherapy.

Disrupted sleep is also associated with a number of other cancer-hospitable terrain imbalances:

• Weakened immunity
• Insulin resistance
• Inflammation
• Impaired digestion and detoxification
• Changes in gut bacterial balance
• Obesity

Sleep disturbance, sleep deprivation and sleep duration are each associated with increases in markers of systemic inflammation.⁵³ Chronic inflammation is linked to higher cancer mortality.⁵⁴

All of these factors can become a self-reinforcing spiral. Chronic inflammation, for example, is linked to sleep disturbance. Cancer treatment itself causes a marked increase in inflammation which can impair sleep (and also result in depression, fatigue and cognitive dysfunction). Impaired sleep can then increase inflammation.

Conversely, evidence shows that people with cancer who get adequate sleep respond better to cancer treatment, function better, have fewer disease symptoms and live longer than people with cancer who have chronic sleep disruption.⁵⁵

For more information, see our Sleeping Well summary.

When we speak of balancing our terrain so that it is less hospitable to cancer, we are referring to our internal environment. The state of our terrain, however, is greatly dependent on exposures and factors from our external environment:⁵⁶

• Nature immersion, such as forest bathing, increases human natural killer (NK) activity, the number of NK cells, and the intracellular levels of anticancer proteins.
• Oxidation is increased by tobacco smoke and by both ionizing and nonionizing radiation.
• Inflammation is increased by smoking and by indoor and outdoor air pollution.
• Immune surveillance is hampered by tobacco and wood smoke.
• Blood circulation, particularly coagulation (clotting) abnormalities, is influenced negatively by tobacco smoke, the worst “clotting offender.”

See the BCCT summary on Creating a Healing Environment for specific measures you can take to enhance positive exposures and reduce your exposures to terrain offenders in your environment.

Having good social support shows up time and again as tipping the balance toward a longer life. How that might influence one’s terrain and the TME is suggested by studies such as one looking at social support, psychological distress and natural killer cell activity in women with ovarian cancer. Compared to those who felt alone, helpless and emotionally distraught, women who felt loved and supported and who kept up their morale had more combative NK cells.⁵⁷

Conversely, social isolation appears to contribute to the chronic stress response. Social support may create a more favorable balance of stress chemistry.⁵⁸

Read more in our Sharing Love and Support summary.

Those of us who have worked for years guiding people with cancer and carefully observing what really matters agree that finding joy, finding meaning, or finding purpose seems to be the essence of living well (and in many cases, living longer than the doctors predicted).

Indeed, every one of BCCT’s integrative oncologist advisors include care of the spirit in their integrative protocols. As Keith Block writes, “Every possible factor influencing the progression of cancer should be explored when you are fighting for your survival. I have seen time after time the difference it [mind-spirit care] makes.”⁵⁹ Some evidence indicates pleasant emotions can produce a physiological response to that can impact immune function, hormonal balance and insulin resistance—three of the five key pathways of disease mentioned above. For example, a 2006 study “revealed that an increase in secretory immunoglobulin A and a decrease in salivary cortisol were induced by pleasant emotions."⁶⁰

Accurately and scientifically measuring the biological effects of meaning or purpose on the tumor microenvironment is difficult, but early evidence shows a relationship between mind/spirit and survival. Researchers have postulated that a distinct personality type (sometimes called “type C”) is possibly at greater risk of developing certain cancers. This personality type is marked by being passive and submissive and minimizing or denying a person’s authentic spirit. These adaptive personality characteristics may favor the development or progression of disease. If so, then working to address these adaptive characteristics may contribute to healing.

Small studies involving people with incurable or metastasized cancer have investigated this line of thinking. Two small studies showed significant increases in survival with psychotherapy. The first correlated extended survival among those who scored higher on these scales:⁶¹

1. Ability to act and change
2. Willingness to initiate change
3. Application to self-help work
4. Relationships with others
5. Quality of experience

In the second study, longer-term survivors displayed a much higher degree of early involvement in their psychological self-help than did most of their nonsurviving peers. The researchers found these common qualities among the survivors:

• Authenticity, a clear understanding of what was important in one's life
• Autonomy, the perceived freedom to shape life around what was valued
• Acceptance, a perceived change in mental state to enhanced self-esteem, greater tolerance for and emotional closeness to others, and an affective experience described as more peaceful and joyous.

The authors hypothesize “to the extent that the progression of cancer, or other chronic disease, is favored by a distorted psychological adaptation such as type C, healing may be assisted by a reversal of that adaptation—in the case of cancer, toward greater authenticity of thought and action.”⁶²

Though mind and spirit will not directly attack cancer, Block asserts that they exert potent indirect influence on the growth and spread of cancer by affecting your internal biochemistry, including molecular factors, and the state of your immune system.⁶³

Meanwhile, anyone caring for and paying attention to the whole person with cancer knows that helping people find meaning and joy might very well be the thread that holds all the swatches together.

For more information, see our Exploring What Matters Now summary.

A flawed myth often promoted by the alternative medicine community is that boosting your immune system through natural or other approaches can eradicate cancer. Dr. Block illustrates this when describing the link between immunity and cancer. He replays the all-too-common scenario of a patient saying, “I’m concerned about the side effects of chemo and radiation. I want to do everything possible to get well, but I would much prefer to treat my cancer naturally, by boosting my immune system. Can you help me?”⁶⁵

Block explains that the immune system is just one of a number of factors influencing cancer. Nor does the immune system automatically identify cancer as a potential threat . . . the longer the tumor has been growing, the more adept it is at escaping the surveillance of the immune system. Furthermore, even if the immune system does recognize cancer cells, the normal immune response may not be adequate to get rid of the cancer. “Since most cancers have been growing for years by the time they are diagnosed, most alternative and even experimental immune-based treatments are ineffective at best, and could delay effective treatment.”⁶⁶

Dr. Block cautions that “you may place yourself at serious risk if you avoid appropriate conventional therapies in the misguided hope that immune manipulation will eradicate your cancer. In most cases, if your cancer is accessible, you are best off having the tumor treated conventionally, and only then exploiting the immune system's resources . . . the more active immune strategies do have an important role, but to date they are more for containing growth or sustaining a remission than shrinking or eliminating tumors.”⁶⁷