Introduction Aside from specific genetic irregularities which confer a propensity towards the development of certain types of Cancer, the general population shares a fairly equivalent risk from environmental exposure, lifestyle, and other factors. Yet even among cigarette smokers, there is not a uniform progression to neoplasia. In our tendency to focus primary attention upon pathology and alleviating cancer patients of their tumor burdens, some important etiologic questions tend to be overlooked:
As far back as 1909, Paul Ehrlich championed the concept that the human immune system functioned to eliminate nascent malignancies. His concept was that immune surveillance occurred at the level of individual cells, and that absent this mechanism of internal defense, Cancer would be rife within the human population. Recently, in the face of continually-rising Cancer incidence and the relative failure of existing therapies to achieve desired cure rates, attention has begun shifting back to the immune system as a key strategic partner in the War against Cancer. Because of this, many medical scientists are looking beyond the standard conceptual framework of administering cytotoxic radiation and chemical poisons. The most promising new research is oriented towards identification of molecular messengers which enhance immune system function by directing its attention to search out and destroy cancer cells lurking within the body, thereby regulating the progression of Carcinogenesis unto Cancer. Carcinogenesis In consideration of the known
cellular biology, it is readily apparent that what we refer to as Carcinogenesis is not itself a disease, nor even wholly a pathologic
process; the pathology of Cancer is only a late phase of Carcinogenesis. By analogy, one can view Obesity and Metabolic Syndrome as latter,
pathologic phases of Appetite— it is the role of an intact Nervous System to provide the signals and functions which enable the body to limit
the progression of appetite to a desirable range of beneficial Alimentation, and it is the role of the immune system is to provide the signals
and functions which enable the body to limit the progression of Carcinogenesis to the range of beneficial cellular growth, maintenance and
proliferation. This last group of transformed cells that forms the pool of candidates for future Cancers, and the charge of the immune system is to prevent their progression unto the malignant pathology of the latter phases of Carcinogenesis. Immunity A growing body of data suggests that granule-containing cells of the Innate Immune System play a significant role in limiting the progression of Carcinogenesis into its pathologic phases. These include Natural killer (NK) cells, Macrophages, Cytotoxic T-cells, and Neutrophils. Among these, the NK cells are bone marrow-derived, large lymphocytes whose cytolytic activity against transformed cells is essential to disrupting the progression of Carcinogenesis during its early, non-pathologic phases. Before cytotoxic T lymphocytes are activated, NK cells mediate innate immunity,
effecting granule-mediated lysis of tumor and virus-infected cells, as well as arbitrating allorecognition. The rapid activation profile of NK
cells is a hallmark of their potency as innate immune system effectors, positioning them as vital players in the aim of Quantum Cancer Extinction— elimination of malignant and pre-malignant species at the cellular level; however, the condition
of Immunosenescence impairs their innate ability to control the advancement of Carcinogenesis. Immunosenescence The observed decline in immune function associated with increasing age is referred to as Immunosenescence in the literature by many thought leaders [1]. Immunosenescence manifests primarily as an insidious, chronic, persistent dysregulation of global immune function, notably involving progressive, systemic depression of cellular immunity. This immune impairment is evidenced by direct inflammatory injury of vital organs, tissues and blood vessels; impaired
responses to antigen exposure, increased infectious disease morbidity and mortality rates; and an increased incidence of autoimmune disorders
[1-4]. Quite surprisingly, these changes are typically of early onset, progressing further as an adult advances
in age. The process of decline may be further exacerbated by the adverse effects of a number of lifestyle and environmental factors,
including: stress, inadequate sleep, poor nutrition and gastrointestinal function, toxic chemical and radiation exposure (including
chemotherapy and radiation therapy). Immunosenescence specifically affects Natural Killer cells
and phagocytic cells in several ways, leading to diminished cell counts and an impairment of cytotoxic activity against transformed cells, including cancer cells. Anti-cancer immunity studies performed on elderly donors
show diminished NK cell cytotoxic activity against reference standard K562 erythroleukemic cells [5]. Additionally, elderly individuals with relative NK cell depression demonstrate a tripled 2-year
mortality risk in comparison to subjects with adequate NK cell levels [6].
Centenarians are generally held as an exemplary model of healthy adult aging, and studies of this select population reveal well-preserved NK
cell cytotoxic function [7]. |
