Immunity and Cancer in Integrative Medicine

Full title: “Aspects of Immunity and Cancer in an Integrative Medicine Context”

Abstract

When considering different medical systems and the approach to biological identity, immunity, and disease processes it is important to determine the meaning of different terms. Biomedicine and Traditional Chinese Medicine use different language that is not exactly translatable for immune system, psyche, nervous system, and in relation to cancer disease processes which can reflect different understandings and approaches to treatment. However, new advances in the field of Oncology (Body Terrain, Tumor Microenvironment, Psychoneuroimmunology) suggest important ways that Biomedicine and Traditional Chinese Medicine intersect and can mutually enhance each other.

Introduction

‘The old body is the one that got sick. You don’t want to return to the old body.’  – Personal Communication, Robert Levine, 2008

The above words are a subtle directive delivered by a seasoned Chinese Medicine practitioner to a patient undergoing cancer treatment. This paper will be an unpacking of these words as they apply to an ‘Integrative Medicine’ context in the treatment of cancer. Here, ‘Integrative’ refers mostly to Biomedicine and Traditional Chinese Medicine. However, the concept can also be used to speak about how research comes together with clinical practice within encounters between practitioners and patients.

Conventional biomedical treatment for cancer has for decades mostly included aggressive treatment against existing cancers (surgeries, radiation therapy, and chemotherapy). However, recently the methods and language of contemporary biomedical cancer treatment have shifted, based on research, to a more ‘holistic’ or ‘integrative’ approach to cancer care – with varying focus on the body’s ‘terrain’, the tumor microenvironment (TME) and the extracellular matrix (ECM), as well as targeted immunotherapies. There is also advancing knowledge of networks of communication like psychoneuroimmunology, which considers a person’s psycho-emotional and psycho-social imbalances as possible contributors to mutations, development, and progression of cancers via mechanisms of the nervous, endocrine, and immune systems. We will briefly consider these developing areas of Oncology in this paper. Included in this research are questions about the human immune system and cancer – does the conventional idea that cancer arises from weakness or malfunction of the immune system really encompass what happens when a body develops cancer?

Along with these considerations of current biomedical cancer care and understandings of immunology, the focus in this paper will be on how these new approaches can be engaged from a Traditional Chinese Medicine (TCM) perspective. How do these current terms of body terrain, tumor microenvironment, extracellular matrix, and psychoneuroimmunology intersect with TCM practice and theory? What does the historical practice of TCM bring to these current conversations that are not included in the biomedical approaches? The field we call ‘Integrative Medicine’ is complex, and it is important to respect all traditions that come to the field and learn to listen in new ways that do not constitute dominance of any one practice or language over another.

Biomedicine

Immunity, Biological Identity, Microenvironments

We begin by asking what constitutes ‘immunity’ in living organisms. The textbook definition of the Human Immune System includes the organs of Thymus, Spleen, Bone Marrow, Lymph Vessels and Nodes, and Cells including T-Cells, B-lymphocytes, macrophages, Natural Killer (NK) Cells, Neutrophils, and Antigen-Presentation Cells.¹ It is conventional knowledge that the immune system functions as a system of defense for the body. However, in the Philosophy of Immunology,² the author sees ‘immunity’ as part of all biological life and urges us to consider ‘immunity’ as a broader function than only ‘defense’ of the organism. The broader view sees immunity developing within ‘ecological and evolutionary contexts’ in relation to other organisms. Within this understanding of immunity as part of contexts and relationships, we can see both ‘innate’ and ‘adaptive’ immunity.^2(p6) Pradeu sees immunity as including not just mechanisms of ‘defense’ (recognition, control, and elimination of pathogens), but also mechanisms of ‘repair’ and ‘development’ (regeneration, clearance of debris, maintenance). In a very general sense, we can say that the immune system provides boundaries and preserves unique biological identity. Pradeu also observes that the way we conceptualize bodily ‘systems’ (including the immune system) are modes of classification that help us delineate physiological phenomena. The systems are not actually as distinct as our classifications are, but rather they are overlapping. Relationships between them are important (e.g. immune, endocrine, and nervous systems). Interrelated physiological mechanisms create ‘immunity’ – ‘one of the main devices ensuring the cohesion of the organism and the delineation of its boundaries. ^2(p13)

This expanded view of immunology informs the understanding of cancer as a ‘de-unification of the individual’ – a failure of the immune system to maintain unique biological individuality.² Cancer results from the ‘dysfunction of the mechanisms that normally insure the cohesion of the multicellular individual.’^2(p30) It is accepted scientific knowledge that cancer involves ‘uncontrolled cell multiplication and the cell’s potential to invade other parts of the organism’.^2(p31) It is also commonly understood that cancer involves a failure of the immune system’s ability to survey and kill abnormal cells. What Pradeu accentuates, however, is that the immune system ‘not only monitors tumors but also shapes them.’^2(p33) This view is informed by research on the Tumor Microenvironment (TME). Minna Bissell, a researcher at UC Berkeley, led research in this field with her lab’s focus on Tumor Microenvironment and Extracellular Matrix (ECM).³ Prior to this collaborative research, the ECM was considered ‘inert’, but they have discovered that the extracellular matrix and the microenvironment of the cell interact chemically and physically. Thus, context, the ‘cellular and tissue architecture’ matters: ‘Gene expression and therefore cell function, changes depending on the context, and the cell’s microenvironment influences these changes.’³

Research following Bissell and Hines⁴ has consequently shifted from tumor-only focus to focus on tumor and microenvironment. Further, understanding of how the immune system may be tolerating a tumor in a local microenvironment (via adaptive immunity) has led to targeted immunotherapies which ‘break the state of immune tolerance’ in local tissue and reignite the immune system to target and eliminate cancer cells.^2(p36) The tumor microenvironment includes the local environment but also immune system organs and microbiota. It is important to understand that elements of the immune system ‘allow the tumor to emerge and grow’.^2(p36) Thus, the immune system doesn’t just kill and eliminate cancer cells but can also maintain and develop tumors. Researchers have been led to ask if cancer is an immune system dysfunction or an ‘abnormal local context’ which influences the immune system.^2(p39) In general, we can understand that cancer is ‘a cohesive multicell organism that can be like an ‘organ’ or ‘wound’ or ‘pathogen’’.^2(p42) Cancer can grow because of an abnormal context as much as a dysfunctional immune system.

Immunity within an Interconnected Network

Another important series of developments in Immunology follow the concept that the ‘Immune System’ (like all physiological systems) does not function separately but more as an integrated system. ‘Whatever forces were operating to set immunology apart, recent data suggest that much could be learned by studying immunoregulation as part of an integrated

network of adaptive processes including behavior’.^2(p43) The term “neuroimmunology’ denotes interaction of the nervous system with the immune system. ‘Psychoneuroimmunology’ includes cognitive aspects, behavior, conditioning of the immune system, mental disorders, and stress related to immune response. These interactions between the nervous system and the immune system can have important functional effects.² Other actors within this integrated system include cognition, and microbiome-gut-brain connections. A picture of a more ‘embodied cognition’ emerges, one that closes the gap between psychology and the rest of medicine. This view of psychological/physiological interactions also reinforces, from a biomedical perspective, the profound wisdom of TCM, which asserts a clear understanding of the two-way street between ‘body’ and ‘spirit’ (Shen). Chinese medicine understands the indivisibility of the physical and the psychospiritual, to which we will return later.

Specific research in the fields of Neuroimmunology and Psychoneuroimmunology, which emerged in the 70’s and 80’s has grown, including in Oncology.² I will consider two studies here that research factors which contribute to the development and progression of cancers. The first, ‘Psycho-oncology and cancer: psychoneuroimmunology and cancer’,⁵ looks at the significance of the immune system for different cancers, which include heterogeneous disease processes. The study focuses on the role of NK (Natural Killer) cells and the role of stress more generally in immune dysregulation, also including cellular DNA repair and apoptosis. In this study, they found that ‘NK cell cytotoxicity can be down regulated by stress, presumably through neuroendocrine mechanisms’.^5(p165) They also found that networks of social support or lack of support can affect NK cell cytotoxicity. The effect of stress on mechanisms of DNA repair and cell apoptosis can also result in suppression of immune function.^5(p166) The study concludes by recommending stress reduction techniques to boost immune function generally.

The second study, ‘Psychosocial Factors and Disease Progression in Cancer,’ considers the relationship of psychosocial factors to both immune responses in phases of early neoplastic changes and in later cancer progression.⁷ The focus was also on the adrenal stress hormones cortisol and catecholamines, which are elevated in situations of acute and chronic stress,^6(p2) and thus starting with ‘negative’ psychosocial factors such as depression, pessimism, repressed emotional expression, and weak social support. They are also working with newer research understandings of the Tumor Microenvironment (TME):

‘Our newly developed understanding of interrelationships among neuroendocrine substances, tumor-growth signaling factors, and immune mediators provides a more complex picture of how psychosocial factors may influence the growth and survival of tumors, particularly within the tumor microenvironment (within and surrounding the tumor)’^6(p1)

On the other side of the emotional spectrum, positive emotional affect as well as social support, etc., have shown to be favorable overall to the patient’s wellbeing:

‘In contrast, optimism, acceptance, using humor to cope, finding positive benefits in the cancer experience, and social support have all been related to longer cancer survival, to neuroendocrine regulation, or to cellular immune parameters including greater lymphocyte proliferation and NK cell activity and greater production of those cytokines (e.g., gamma-interferon) that orchestrate complex immunologic responses against tumors.’^6(p3)

Again, as in the previous study, stress management techniques that increase ‘positive psychological experiences’ are recommended, especially during treatment-related immunosuppression.^6(p4)

These are two examples of research, the arena where scientists explore new edges of science and communicate their findings in technical and precise language. In contrast, clinical practice is the space where crucial communication between patients, their families, and physicians and other healthcare providers take place. If, as Chinese medicine holds, all health and disease have a psycho-emotional aspect (involving Shen), then the space of clinical practice involves communication about potentially life-saving changes that need to happen. This communication can be both verbal and non-verbal. It can also involve communication between different practitioners. In Life over Cancer, Dr. Keith Block communicates about cancer beyond technical scientific papers but still uses the language of ‘microenvironments’ and the body’s ‘terrain’. His writing about cancer and healing from cancer shifts from the focus on ‘single targets’ (as in conventional treatment) to seeing cancer as a systemic imbalance – ‘a tumor is merely the most obvious symptom of an altered, unbalanced system.’^7(p2) Furthermore, the imbalance must be addressed beyond the tumor to prevent recurrence. Cancer is an underlying condition. He writes a kind of warning to patients in a clinical tone:

‘This means that cancer is a systemic disruption and perversion of the body’s resources and mechanisms. Because cancer will try to use every bit of your body’s biochemistry to proliferate, you must strengthen every biochemical defense possible to defeat it.^7(p3)

And in words which echo what the first TCM Practitioner said:

‘You must change the environment that nurtured the cancer in the first place.’^7(p19)

On the website ‘BCCT – Beyond Conventional Cancer Therapies’, Michael Lerner also communicates in a more clinical manner along similar lines, specifically about Body Terrain and the Tumor Microenvironment. The Body’s Terrain is a ‘seed and soil’ metaphor – the terrain is the internal environment, including the Tumor Microenvironment. Cancer takes hold within this terrain. ‘Cancer is a complex mixture of cancer cells, normal blood cells, tissue, and immune cells.’⁸ Aspects of ‘modifying the terrain’, ‘creating a body that cancer doesn’t like’ includes issues of the immune system, inflammation, hormonal balance, insulin resistance, digestion, and detoxification. The terrain also includes a network of communication named ‘psychoneuroimmunology’, as previously discussed.

Traditional Chinese Medicine

Cancer and Immune System

The conceptualization of the body’s terrain, now gaining traction in biomedicine, is very comprehensible from a TCM perspective which always involves a ‘terrain’ – an ecology, a balancing of imbalance, clearing what is excess and nourishing that which is deficient. Lerner makes this connection; ‘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.’ In TCM language, we say that we must treat the root as well as the branch.

Within the tradition of Chinese medicine, there has been a medical understanding of growths, stones, and tumors dating back to The Yellow Emperor’s Classic.⁹ The principle causes of these conditions were understood as qi stagnation, blood stagnation, excess climactic heat and cold, and emotional factors. Due to some combination of these conditions, pathogens accumulate, and tumors develop.⁹ Within the classical tradition, Hua Tuo thought surgery would be necessary for these conditions if they could not be treated by needles or herbs.⁹ Li Gao emphasized the need to strengthen digestive qi while also attacking the tumor.⁹ It was also emphasized that both deficient and excess aspects of the disease needed to be addressed.⁹

In a broad sense, cancer in TCM is understood as a disease process that is a struggle between Zheng Qi (Upright Qi) and Xie Qi (Sickness Qi). In this struggle, an actualized cancer has a ‘life force’ that wants to live. (Personal Communication, Dr. Erlene Chiang, 2020) Zheng Qi is ‘a general term to describe the various forms of Qi that protect the body from exogenous pathogens. Usually only used when contrasting the strength of the body’s Qi with the strength of invading pathogen.’¹⁰ The term ‘Zheng qi’ is not identical to ‘immune system’ but is related – ‘Healthy qi (Zheng Qi) is the integral manifestation of the human body’s immune functions’¹⁰ and is related to the various Zang organ Qi: Kidney (Jing Qi, Yuan Qi), Spleen (Ying Qi, Gu Qi), and Lung (Zong Qi), as well as to Wei Qi – which is the body’s defensive Qi more at skin level.

One TCM author suggests a new term for the TCM lexicon that would more closely match biomedicine’s ‘immune system’: ‘Nei Wei Qi’ (internal defensive Qi).¹ She suggests that we think of Nei Wei Qi as part of the Zheng Qi of the body, coming from Yuan (Source) Qi, belonging to Yin and Qi, running through the entire body, and ensuring the functioning of Zang Fu.¹ The functions of Nei Wei Qi would closely match the biomedical immune system: defense (recognizes, mobilizes, attacks, eliminates Xie Qi), surveillance (attack and eliminate cancer cells), and tolerance (differentiate foreign from self). This new term could be integrated into TCM tradition and help with Integrative Medicine conversations and practices.¹

The TCM view of the body is based on integration and balance – a balance that all TCM treatment strives to restore. This integral balance is the source of the body’s defense and cohesion: ‘The concept of holism is the main characteristic of TCM immunology…This integral stability and harmony is the root of disease defense and health maintenance.’¹⁰ If health is a function of balance, then disease arises from disharmony, and the basic harmony/disharmony is between Yin and Yang forces.

Shen, Psyche, Emotion

Let’s shift to consider how the conceptualization in biomedicine of ‘psychoneuroimmunology’ translates into or resonates with TCM. Giovanni Maciocia has written a 600-page text on the Psyche in Chinese Medicine,¹¹ so we can only briefly consider a few points here. How do we conceptualize ‘Psyche’ (a Western concept) from a TCM perspective? The word ‘Shen’ can refer to the spirit that resides in the Heart but can also be a more encompassing term that includes the 5 Shen based in the Yin organs and can mean the whole psycho-somatic being. ‘Spirit’ may be a good translation of this word as it refers to the ‘spiritual complex of Yin organs (including Heart-Mind).’¹¹ Chinese medicine begins with a different framework than Western medicine, which has inherited the Cartesian separation of ‘body’ and ‘mind’. As Maciocia reminds us: ‘As any practitioner of Chinese Medicine knows, the unity of spirit and body is a distinctive and central feature of Chinese Medicine.’^11(p4) In the Western framework, ‘mind’ is more related to brain, and ‘spirit’ has the connotations of a transcendent aspect, a ‘soul’, which is ‘trapped’ in the body, but not of the body. In the Chinese medicine worldview, all the world is a manifestation of Qi, in flow and constant transformation. ‘Both Spirit and body are manifestations of Qi, the spirit being the most rarefied form.’^11(p4) There are two basic forces that shape ‘Qi’ – ‘Condensation/Yin Force/Body, and Dispersal/Yang Force/Spirit.’¹¹ Maciocia elegantly describes the basic difference between the two medical views:
‘Of course, Western medicine recognizes the interrelationship between the mind and the body too, but its way of doing so differs from that of Chinese medicine. The Western view of the mind-body integration is essentially like a top-down pyramid from the mind to the body. In other words, emotional stimuli induce changes in the autonomic nervous system, which will affect the viscera. In Chinese Medicine, it is more of a 2-way interaction between ‘brain’ or ‘mind of the heart’ (Shen) and the viscera. Disharmony can be affected in both directions. Two poles of same substance, Qi, and emotions take place at the same physical and psychic phenomena.’^11(p7)

We also use the word ‘emotion’ in TCM, but often in relation to the etiology of disease – ‘the 7 emotions’. There may be a translation issue here as well. For ‘qing’ or ‘ci ji’, ‘passion’, with the sense of being ‘carried away’ may be a more appropriate word.¹¹ As in all aspects of health, Chinese medicine emphasizes balance for mental-emotional aspects. The etiology of disease arises from (excess?) emotions which impair circulation of Qi and disturbs the Yin organ spirits. Each emotion (or excess emotion, or passion), arising from the psychic fields of each Yin organ, will affect circulation of Qi differently. This in turn ‘alters the balance of internal organs and harmony of Qi and Blood’.^11(p116) ‘The mutual interaction between the emotions and the Internal Organs and the unity of body and mind is one of the most important and distinctive aspects of Chinese Medicine.’^11(p116) Again, the two-way street: emotional stress can cause organ imbalance and organ imbalance can cause emotional stress.

On an even deeper level than translation, the concept of emotion and Psyche in Western culture arises from a different sense of ‘self’ than that embodied in the Chinese medical tradition.¹¹ Chinese medicine has been profoundly shaped by Confucianism, where the ‘self’ is defined by the social role within community. In a Confucian perspective, ‘emotions’ are more ‘social and ethical’, not psychological and individualistic as in the Western sense. Emotions should be balanced so one can perform their social role, not examined for psychological roots. So, we are left considering Chinese Medicine as a system containing a brilliant view of body/mind unity and also encompassed by a Confucian social model, which may not be a helpful orientation for Western patients. This presents another dilemma for ‘Integrative Medicine’.

Conclusion – Questions for Integrative Medicine

I hope that this brief meditation on Immunity in relation to cancer from both Biomedical and Chinese medicine perspectives highlights some of the insights and challenges that emerge in an Integrative Medicine context. Chinese medicine offers a profound view of the indivisibility of ‘body’ and ‘spirit’ that Western medicine is only starting to comprehend. However, the research capacity of Western science gives us current and precise information that we don’t have in Chinese medicine such as understanding of Tumor Microenvironments or specific mechanisms involved in psychoneuroimmunology. Additionally, we are taught TCM concepts in abridged textbook forms that really need further elucidation from Classical scholarship, such as the concept of ‘Zheng Qi’. The work of finding useful theoretical and clinical approaches in an Integrative Medicine context is ongoing.

How was it that the Chinese Medicine practitioner found a way to imprint on his patient’s consciousness the importance of changing the very terrain of her body? He had interpersonal skills and clinical expertise made of trust, timing, and resonance – subtle skills that bring the insights of research into the beautiful communication of practice.

REFERENCES

1. Chen Y. Nei Wei Qi Represents Immune System in TCM, Part 1, Acupuncture Today, May 2008, Vol. 09, Issue 05.
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4. Bissell MJ, Hines WC. Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nature medicine. 2011; 17(3), 320–329. https://doi.org/10.1038/nm.2328
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6. Antoni MH, Lutgendorf S. Psychosocial factors and disease progression in cancer. Current Directions in Psychological Science. 2007; 16(1), 42–46. https://doi.org/10.1111/j.1467-8721.2007.00472.x
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8. Beyond Conventional Cancer Therapies. Retrieved August 16, 2020. https://bcct.ngo/
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