Body Terrain and the Tumor Microenvironment

Cancer cells do not act alone. They enlist the body’s normal cells, molecules, and blood vessels in their efforts to survive, metastasize, and acquire drug resistance.

Memorial Sloan Kettering Cancer Center1

Key Points

  • The recognition of the whole body's role and interactivity with cancer cells is an ancient concept that is currently gaining traction in mainstream medicine.
  • Malignant and nonmalignant cells interact to create the tumor microenvironment.
  • Cells in the tumor microenvironment plan a key role in cancer’s development, spread and response to treatment.
  • Modifying your body terrain to make it inhospitable to cancer is one of the most important actions you can take. However, these actions alone are not enough to control or cure cancer.

Definitions

  • Terrain: from the French word terrein—ground or land, especially their physical features. In integrative medicine circles (especially in Europe) terrain denotes the physical features and state of a person’s body and the influence of that state on health and disease prevention. “It is the sum total of diet, lifestyle, metabolism, environmental exposures and stress.”2
  • Tumor Microenvironment (TME): “The normal cells, molecules, and blood vessels that surround and feed a tumor cell. A tumor can change its microenvironment, and the microenvironment can affect how a tumor grows and spreads.”3

“The study of terrain is beginning to gain traction in mainstream cancer research.”4 However, the concept is not new: traditional Chinese medicine (TCM) has viewed terrain as important for millennia. Viewing cancer as a systemic disease and the tumor as a symptom of that disease, TCM considers that to heal the disease, the underlying constitution must be altered.

Integrative oncologist Keith Block, MD, more specifically focuses on the “biochemical terrain” and whether or not that biochemistry is balanced or disrupted and therefore inhospitable or hospitable to cancer.5

For the purposes of this summary, we consider the terrain as the internal environment of the human host and the tumor microenvironment existing within and influenced by the host’s terrain.

Importance of the Microenvironment

In recent years, we’ve had to let go of the notion that cancer is just a mass of malignant cells or simply a disease of aberrant genes—if so, we would have long ago succeeded in eliminating or curing cancer by removing or destroying cells or targeting genetic mutations. Rather, cancers are “complex ‘rogue’ organs, to which many other cells are recruited and can be corrupted by the transformed cells.”6

Malignant and nonmalignant cells interact to create the tumor microenvironment (TME). “The nonmalignant cells of the TME have dynamic and often tumor-promoting functions at all stages of carcinogenesis.”7 More simply put: “Cancer is a complex mixture of cancer cells, normal blood cells, tissue and immune cells. Tumor cells themselves alter the microenvironment to secrete things that help tumors grow.”8

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Terrain as Soil

When it comes to understanding the tumor microenvironment and how to create a body in which cancer can neither thrive nor survive, a few gardening concepts provide a good analogy. Cancer is the seed and the body is the soil that cancer might try to use as a growth medium. Your terrain is the body’s/soil’s internal environment.

Chemotherapy, radiation therapy and surgery are focused on killing or removing the cancer seed, which we treat like a weed or pest. Gardeners know that a pesticide or weed killer won’t work if you’ve mischaracterized the pest or weed and used the wrong pesticide, or if you used a pesticide that the pest or 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 microorganism and biochemical balance favors the growth of plants and deters pests from taking hold.

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 inhospitable to cancer.

Our body’s relationship with cancer is not too different. No matter how powerful our treatments are at killing the cancer (the seed), 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.

Same Soil, Different Outcome?

“Cancer is not an isolated group of errant cells waiting passively to be annihilated by a wonder drug. . . Cancer does not present a single target for a magic bullet; a tumor is merely the most obvious symptom of an altered, unbalanced system. . .And that’s why both the new targeted therapies and the older weapons of surgery, radiation and old-line chemotherapy so often fail to prevent the spread or recurrence of the disease. . . They neither pick up renegade cancer cells, strengthen the body’s biological balance, nor reach all of the underlying molecular accidents that initiated cancer in the first place. . . As a result, even if the original tumor is gone, this biological imbalance creates an environment for cancer to recur: tumor cells use the body’s healthy resources to grow and multiply.”9

Our Soil, Ourselves

We’ve tended to focus on the cancer, but its host tissue—the soil, rather than the seed—could help us predict the danger the cancer poses. If we look at the soil, as well as the seed, “it would return us to the true meaning of ‘holistic’—to take the body, the organism, its anatomy, its physiology—this infuriatingly intricate web—as a whole . . .It would help us understand when you have cancer and when cancer has you. It would encourage doctors to ask not just what you have but what you are.”10

This profound quote from Dr. Mukherjee, author of The Emperor of All Maladies, provides a remarkable insight: If we come to know a person’s soil, their terrain, we can understand why cancer could take hold in them in the first place, predict how dangerous that cancer is to the patient if things don’t change, and then create an individualized treatment approach that targets the seed while it tends the soil.

Tending Your Terrain

Many of our therapy summaries include references to tending the terrain, the seed and soil, the tumor microenvironment and making the terrain inhospitable to cancer. Indeed, many of the healing practices that are part of a healthy lifestyle contribute to making the body inhospitable to cancer, and therein may lie their value in helping delay or reduce risks of cancer recurrence. In addition, these practices may also stave off other conditions or illnesses typically spawned from treatment toxicity, such as cardiotoxicity.

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Modifying the Terrain

Naturopathic oncologist Lise Alschuler and co-author Karolyn Gazella write about creating a body that cancer doesn’t like. They describe five key pathways that have the greatest impact on whether we are healthy or become sick:

  • The immune system
  • Inflammation
  • Hormonal balance
  • Insulin resistance
  • Digestion and detoxification

They go on to describe five core strategies and corresponding action steps that positively influence the key pathways:

  • Enhance your spirit
  • Let’s move
  • Enrich your diet
  • Utilize dietary supplements
  • Create rejuvenation

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Inflammation: An Example

Using inflammation as a subject, studies and meta-analyses have found that those with the highest pre-diagnostic levels of C-reactive protein (CRP)—a marker of chronic inflammation—have higher rates of cancer than those with lower levels:

  • Breast cancer16
  • Colorectal cancer risk17 and mortality18
  • Lung cancer and all cancer19
  • Prostate cancer20
  • Renal cell carcinoma21
  • Urologic cancers: bladder, penile and upper tract urothelial carcinoma22

Moreover, “changes in post-treatment CRP serum levels have also shown promise in determining survival.”23 Reducing C-reactive protein even after diagnosis and treatment can enhance survival.

Blood Sugar and Insulin: Another Example

Other studies and reviews investigating blood sugar and insulin find a relationship with cancer risk and progression:

  • All cancer24
  • Breast cancer25
  • Colorectal cancer26
  • Endometrial cancerD27
  • Melanoma (lower risk)28
  • Pancreatic cancer29
  • Prostate cancer risk (both higher and lower) and mortality30

Balancing each of the above six terrain features, according to Block, helps to deal with the five major challenges of having cancer:

  • Reducing tumor growth and spread
  • Reducing tumor bulk and improving treatment response
  • Tolerating conventional treatment
  • Optimizing daily functioning
  • Reducing the risk of life-threatening complications

Dr. Block describes how to determine which aspects of your internal terrain you most need to target, providing protocols for addressing each terrain feature as well as a general protocol for broad-spectrum terrain support supplementation.31

Your Microbiome

Many trillions of microorganisms live in and on us, many of which are in our gut―in fact, non-human microbe cells in our bodies outnumber our human cells. Over thousands of years, our bodies have developed a symbiotic relationship with these organisms, generally supporting each other’s health and well-being. In exchange for food and lodging, these microorganisms:32

  • Help with digestion and produce essential vitamins and minerals
  • Support intestinal wall integrity
  • Influence our sleep cycles and immune system
  • Signal to each other to affect functions
    • Metabolism
    • Inflammation system
    • Brain and nervous system
    • Immune system

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The 7 Healing Practices: Modifying the Terrain

The Hallmarks of Cancer and the Tumor Microenvironment

Scientists Douglas Hanahan and Robert Weinberg created a framework called the Hallmarks of Cancer. These hallmarks are the biological capabilities that cancer cells acquire as they go through a multi-step process of developing into tumors.38

The following list of hallmarks is “sequenced roughly in the order in which these capabilities are acquired by most cancers.”39

  1. Genomic instability: Unstable DNA helps cancer cells “acquire a selective advantage over neighboring cells, enabling outgrowth and dominance in the tissue microenvironment”, especially important in tumor initiation and promotion.40
  2. Sustained proliferative signaling: Cancer cells become self-sufficient and able to grow uncontrollably.
  3. Evasion of anti-growth signaling (evading growth suppressors): Cancer cells no longer respond to antigrowth signals.
  4. Resisting apoptosis (programmed cell death): Cancer cells are able to circumvent the cycle of programmed cell death (apoptosis). Normal cells submit to apoptosis when they are no longer needed or might be harmful to the body.
  5. Replicative immortality: No limits exist on the cancer cell to reproduce over and over.
  6. Deregulated metabolism (cellular energetics): Cancer cells shift from producing energy in the mitochondria to inefficiently fermenting glucose within the cell itself.
  7. Tumor-promoting inflammation: The chronic inflammation microenvironment is associated with cancer formation, growth and transformation as well as apoptosis evasion, survival, invasion, angiogenesis and metastasis.41
  8. Immune system evasion (avoiding immune destruction): Cancers evade immune attack through several mechanisms.
  9. Tumor microenvironment:  At this point, the tumor is primed to use the microenvironment to grow and spread.
  10. Inducing angiogenesis: Cancer uses normal cells to create a blood supply to bring in nutrients and remove waste.
  11. Activating tissue invasion and metastasis: Cancer’s most deadly ability arises, spreading to other organs.

Except for the few inherited cancers derived from a genetic defect (germline mutation), most cancers start off as normal cells that eventually acquire alterations (mutations) in their DNA and essentially “learn” or acquire biological abilities that promote their growth, survival and spread.

These Hallmarks of Cancer are accepted by scientists and clinicians as the foundation for understanding the biology of cancer. Furthermore, many of today’s cancer treatments are designed to target one or more of the hallmarks of cancer. For example, agents such as Bevacizumab (Avastin) and Sunitinib (Sutent) inhibit angiogenesis.42

The hallmarks are focused specifically on the biology and behavior of cells, but the tumor microenvironment is intertwined with the ability of cancer to acquire and maintain the biological abilities to seed, grow, survive and spread. Under the right conditions, the cancer can hijack the microenvironment for its own use.

Consideration of the microenvironment is so vital that an international task force of 180 scientists participating in the Halifax Project suggested that the tumor microenvironment be added as a Hallmark of Cancer. The Halifax project was concerned that our current model of cancer care is becoming completely out of reach for many people in the world. Specifically, they were honing in on the problems of conventional targeted therapies (such as Keytruda, Avastin, and so on.):

  • High costs
  • Short relapse-free period
  • Dose-limiting and combination-limiting toxicities

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The 7 Healing Practices can actually modify many of the terrain factors that nourish the tumor microenvironment.

Eating Well

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.

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Moving More

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.

Managing Stress

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.

Sleeping Well

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

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Sharing Love and Support

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 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.56

Conversely, social isolation appears to contribute to the chronic stress response. Social support may create a more favorable balance of stress chemistry.57

Read more in our Sharing Love and Support summary.

Creating a Healing Environment

When we speak of balancing our terrain so that it is inhospitable 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:58

  • 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 smoking.
  • Blood circulation, particularly coagulation (clotting) abnormalities, is influenced negatively by smoking, the worst “clotting offender.”

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

Exploring What Matters Now

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).

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Terrain Is Important but Not a Panacea

Both cancer treatment to address the tumor and terrain modification to make the body less hospitable to recurrence are called for.

Modifying your biochemical terrain, alone, is not enough to control or cure cancer. On the other hand, conventional cancer treatments alone will not consistently keep the cancer from coming back.64 Generally, both cancer treatment to address the tumor and terrain modification to make the body less hospitable to recurrence are called for. Over and over again, we return to the point that an integrative approach may provide the best chance of exploiting cancer’s weaknesses.

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Written by Laura Pole, RN, MSN, OCNS, and reviewed by Nancy Hepp, MS; most recent update on October 10, 2018.

Highlighted Video


Brian Bouch discusses integrative oncology, part 1

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View All References

More Information

Articles

Books

Professional Journals on the Tumor Microenvironment

  • Tumor and Microenvironment: a quarterly open access journal published by Wolters Kluwer|Medknow on behalf of the Primary Co-Development Institute of Medical Research, Beijing.
  • Cancer Microenvironment: Cancer Microenvironment is the official journal of the International Cancer Microenvironment Society (ICMS).
  • Journal of Translational Medicine: Cancer Microenvironment Section: The Cancer microenvironment section publishes research on the cellular and molecular components of the cancer microenvironment, with a particular focus on translational research that has important implications for the prevention, diagnosis and treatment of human neoplasms.

Video

  • The C-Word: neuroscientist David Servan-Schreiber discovered his own brain tumor during MRI research. He set out to gather as "much information as I could to see what I could do to help my body fight and resist cancer."

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