For decades, since first observing spontaneous tumor regressions in experimental animals, scientists have debated the existence of a surveillance role for the normal immune system (NIS) in regulating the growth and spread of human cancer.1 The observation led to the concept that through surveillance, the NIS could detect and destroy newly formed cancer cells. This concept persists in spite of the fact that 90% of the most common cancers, carcinomas, occur in a host with a fully functioning NIS.2 In addition, there is no good evidence of an increase in common carcinomas in the presence of severely decreased immune function.3
Most public exposure to alternative medicine (AM) comes through popular media, well-meaning friends and relatives, and books by AM practitioners and proponents. One such book is Burton Goldberg’s Alternative Medicine; A Definitive Guide to Cancer.4 In the book, proponents claim that the immune system is an innate “healing system,” and that cancer develops because the NIS is somehow damaged or unable to carry out its “surveillance” role because of defective diet or environmental toxins. Readers are offered reversal of such damage by detoxifying, stimulating, rejuvenating, augmenting, and reactivating the defective NIS. A few AM treatments recommended in the Definitive Guide are: Contreras metabolic therapy with Laetrile, proteolytic enzymes, vitamins, minerals, coffee enemas (p.126); homeopathy (p.147); Carnivora, extract of the Venus Flytrap plant (p.60); I. Wm. Lane’s shark cartilage (p. 862); Burton’s Immuno-augmentive Therapy (p.883); Wheeler’s “Autogenous Vaccine” (p.893); Siegel’s mind/body treatment modalities (p.389); Munozi’s antimycoplasma autovaccine and removal of dental toxins (p.897); Spiegel’s emotional support and self-expression therapy (p.459); and Gonzalez’s therapy including detoxification with coffee enemas, dietary supplementation, and proteolytic enzymes (p.778).
THE REALITY OF IMMUNE SURVEILLANCE OF CANCER
The concept that the NIS watches out for and defends against cancer came about as researchers were unraveling and defining the complex chain of reactions that make up this system.5 Immunologists demonstrated that the most common cancers flourished in a host with a fully functional and competent immune system.6 In spite of this, many researchers, as well as “alternativists,” continue to claim that a defective immune system is responsible in some way for development of cancer.7 The “alternativist” rationale is based on two assumptions. First, that cancer cells are produced constantly or intermittently during life. Second, that to protect the individual from a lethal outcome, the immune system must detect, attack, and then destroy each cancer cell as it appears.8
The Normal Immune System (NIS)
While cancers associated with viral infections arise rather quickly, most common cancers develop over many years as the cells escape from normal intracellular control mechanisms via multiple mutations.9 Although tumor cells demonstrate abnormal growth, they still display normal antigenic surfaces. Since the NIS is programmed to recognize “non-self,” it does not “see” the tumor.10
An immune response takes place when foreign proteins, i.e., antigens from non-self cells–major histocompatibility complexes (MHCs) and other minor antigens—are presented to T-cells. The hallmark of the NIS is its ability to respond to this presentation. NIS cells have biochemical properties uniquely suited to generate a large variety of individual receptor molecules (immunoglobulins) and to select those that will be needed for further expression. Thus there exists a seemingly infinite variety of specific receptors produced by immune system cells to which foreign proteins can bind.11
Only by externally manipulating the NIS pharmacologically or by injecting manipulated products can an effective response be induced.12 In spite of the enormous amount of information amassed about the nature of the NIS and the mechanisms by which it acts, immunotherapy still holds only a suggestion of being able to control human cancer.
“Natural immunity” (NI) is immune activity not requiring deliberate immunization by a foreign antigen.13,14 The NI reaction differs from the NIS’s response to protein determinants in that it is not dependent on transplantation antigens found on foreign (non-self) cells. The NI response is due to nonspecific triggering of the activity of cells like natural killer cells, macrophages, or polymorphonuclear leukocytes (PMNs).
Dendritic cells (DCs) are thought to be sentinels of the immune system.15,16 They originate in the bone marrow and are seeded into nonlymphoid tissues. DCs capture and process exogenous antigens for presentation as peptide-MHC complexes at their surface. They facilitate activation of natural killer (NK) cells.17 The NI acts on antigens from infectious organisms and against some antigens present in food or in the intestinal flora.
Because of their ability to attach foreign antigens and to present them to T-cells, DCs are being considered for use as adjuvants for triggering an immune response to cancer cells.18 The program is something like the following: In order to get the NIS to identify and attack the cancer, DCs would be generated in vitro and antigenic material or DNA from the tumor would be attached to them. The antigen-laden DCs would then be reinjected into the patient where they would present the tumor antigen to T-cells. The hope is that through chronic infusion of primed DCs, one can be immunized against one’s own cancer.
But there is also a problem of numbers.19 The average number of cancer cells present at detection of the primary or metastasis is between 1 × 109 and 1 × 1012 cells. Each tumor cell would have to be contacted directly and destroyed by one or more T-cells, and the required number for optimal cancer cell kill is unknown. Even on a 1:1 (killer cell:tumor cell) basis, destruction would require 1 × 109–12 killer cells. There are about 2–4 × 107 total T-cells normally present in an average human.
If enough primed T-cells could be mobilized, they would be diffused throughout the body and there is no known normal mechanism to assure their reaching a critical number of target cancer cells before dying or becoming deactivated.*
THE NIS AND THE MIND
“Alternative” practitioners claim that the mind and “spiritual harmony” promote “healing” by stimulating the activity of the NIS. Their literature asserts that virtually every psychological variable influences NIS surveillance.20 One might conclude that the unhappy, the asocial, and the depressed are the ones most likely to become ill. But clinical studies show that most cancers strike blindly and progress despite mood, personality, or conscious efforts to remain healthy.
At this time, there is no single valid measure of immune competence. There are indirect indices, including simple blood counts and skin tests related in complex ways to overall ability to resist some diseases, mainly infectious. We also know that prolonged stress, fatigue, starvation, etc., can temporarily alter the level of some components of the NIS. But there is no convincing evidence relating such changes to cancer.
It is important to recognize that evidence against an anticancer surveillance role for the NIS is based on research specifically designed to find a correlation between the NIS and spontaneous tumor development. Further, there are no credible reports in the scientific literature to support the contention that “alternative” methods operate—on cancer or on any other disease—through an immune mechanism. Regardless of the means used to evoke an antitumor response, evidence available from clinical and animal studies clearly shows that only after the NIS has been attracted by some external or medical manipulation is there any recognition by the NIS of the existence of autologous tumor cells.21 No “alternative” treatment has been shown to effect such recognition or cell destruction.
Evidence amassed over the past thirty years provides an answer to the question, “Does any AM treatment stimulate the NIS and cause it to identify and destroy new cancer cells when they appear?” The answer clearly is no.
* Molecular chemotherapy as methotrexate can be effective at a minimum of 1 × 10–8 Molar concentration, which is about 1 × 1016–17 molecules of drug per dose. Several orders of magnitude more molecules can be given in high dose chemotherapy. Although many chemical “hits” per cell are probably necessary for effect, the difference between adequate numbers of killing lymphocytes possibly mobilized and adequate numbers of molecules already available in a standard dose is enormous. The normal, nonmanipulated immune system is simply inadequate to the task, and is yet another reason why response to the nonmanipulated NIS has not been described. (Chabner and Myers, Clinical pharmacology)
- Burnet FM. The concept of immunological surveillance. Prog Exp Tumor Res. 1970; 13: 1–23.
- Wick M et al. Antigenic cancer cells grow progressively in immune competent hosts without evidence of T-cell exhaustion or systemic anergy. J Exp Med. 1997; 186: 229–238.
- Joklik WK, Willett HP, Amos DB. Immunity to tumors and pregnancy. In: Zinsser Microbiology. Norwalk, CT: Appleton-Century-Crofts; 1984.
- Diamond WJ, Cowden WL, Goldberg, B. Alternative Medicine: A Definitive Guide to Cancer. Tiburon, CA: Future Medicine Publishing; 1997.
- Hellstrom J et al. Demonstration of cell mediated immunity to human neoplasms of various types. Int J Cancer. 1971; 7: 1–16.
- Green MJ et al. Regulation of the immune response to tumor antigens. J Immunology. 1977; 119: 757.
- Spiegel D. Psychological aspects of breast cancer treatment. Semin Oncol. 1997; 24: 1, Suppl. 1, 36–47.
- Diamond, Cowden, and Goldberg, Alternative Medicine.
- Klein G et al. Evolution of tumors—a review. Nature. 1985; 315: 190–195.
- Hermans IF et al. Antigen expressed on tumor cells fails to elicit and immune response,
even in the presence of increased numbers of tumor-specific cytotoxi T-lymphocyte precursors. Cancer Res. 1998; 58: 3909–3917.
- Lanzavecchia A. Identifying strategies for immune intervention. Science. 1993; 260: 937–944.
- Rosenberg SA. A new era of cancer immunotherapy: converting theory to performance. CA—A Cancer Journal for Clinicians. 1999; 49(2): 70–73.
- Kripke ML, Immunoregulation of carcinogenesis: past, present and future. J Natl Cancer Inst. 1988; 80: 722–728.
- Stutman O, Cuttito MJ. Natural Cell Medicated Immunity Against Tumors. Herberman RB, ed. New York, NY: Academic Press; 1980: 431–432.
- Sallusto F et al. Dendritic cells use macro pinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatability complex class II compartment: down regulation by cytokines and bacterial products. J Exp Med. 1995; 182: 389–400.
- Austyn JM. New insights into the mobilization and phagocytic activity of dendritic cells. J Exp Med. 1996; 183: 1287–1292
- Steinman RM. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991; 9: 271–296.
- Schuler G, Steinman RM. Dendritic cells and adjuvants for immune mediated resistance to tumors. J Exp Med. 1997; 186: 1183–1187.
- Chabner B, Myers C. Clinical pharmacology of cancer chemotherapy. In: Cancer: Principles and Practice of Oncology, De Vita V, Hellman S, and Rosenberg SA, eds. 1993. Philadelphia, PA: JB Lippincott.
- Diamond, Cowden, and Goldberg, Alternative Medicine.
- Stutman and Cuttito, Natural Cell Medicated Immunity Against Tumors.