Page 1, 2, 3
Despite advances in cancer treatment achieved over the last decades, it still remains a failure where the outcome of standard and especially palliative treatment is often poor due to cancer cell resistance. However, in these past few decades, we have assisted in a series of articles in international publications from many countries, proclaiming that our own immune system is now a new weapon against cancer. This has become the fourth pillar of oncology after surgery, chemotherapy, and radiation.
|Townsend Letter provides a platform for those examining and reporting on functional and integrative medicine. Please support these independent voices.
One particular immune cell has gained more interest over the past two decades from researchers: the natural killer (NK) cell, which seems to play a crucial role in cancer.
A number of publications and published scientific papers demonstrate the association between the NK cell and cancer, particularly breast cancer.1 Boosting the NK cells increases the killing of cancer and presents a significant advantage both in the prevention and treatment of cancer.2
Among many available compounds investigated, one has commonly been the subject of publication for its efficacy to activate NK cell activity and for the killing of cancer cells in vitro and in vivo. This compound is known as rice bran arabinoxylan compound (RBAC). It has been widely investigated especially over the past 25 years by scientific researcher M. Ghoneum, PhD, from Drew University in Los Angeles, California. This researcher has spent most of his professional life studying NK cell activity and substances that are able to modify immune function.
According to Dr. Ghoneum, RBAC is the most powerful compound we have to activate immune cells, particularly NK cells. But we are going to see that RBAC not only increases NK cell activity but has other qualities as an anticancer agent. In some studies, patients that were treated with RBAC in addition to conventional therapy (CT) compared with those treated with CT alone showed less recurrence of cancer, higher survival rates, and improved quality of life (QOL).
Various animal studies and human clinical trials, including different types of malignancies, have demonstrated that RBAC is a potent biological response modifier (BRM), being a safe compound with no toxicity that does not exhibit hypo-responsiveness.
It was only around 1990 when I discovered the newly developed rice bran arabinoxylan compound from my Japanese contact in Tokyo and learned about natural killer cells that I started studying NK cells and began to include this compound in my cancer protocol. The more you read about NK cells, the more you understand about the necessity to activate these unique immune cells to increase the death of cancer cells. Twenty-eight years is a long time, and it has permitted me to experiment with various protocols and compounds with cancer patients. You can imagine what I have accomplished during this period and how many cancer patients I have treated in my clinic. Of course, we always expect that what we use offers some efficacy, but this article will show what RBAC is able to do. You can read reports explaining how RBAC increases NK cell activity, and how a tumor can decrease in size, or that tumor markers decrease; but if you directly witness the results with your patient, it may better convince you.
What Are NK Cells and Their Role in Cancer?
Natural killer cells were first discovered in humans and mice in 1975 and were initially identified as unique lymphocytes distinct from B and T cells, being critical to the innate immune system but also bridging the innate and adaptive immune systems. NK cells are known to differentiate and mature in the bone marrow, lymph nodes, spleen, tonsils, and thymus, where they then enter into the circulation. They are a large granular population of leukocytes that can directly kill virus-infected cells or tumor cells.3 Today NK cells are viewed as our first line of defense against intruders and cancer. As we age, NK cells lose their functionality thus leaving us with more vulnerability to viral diseases and especially cancer, which could be one cause of increased cancer rates in aged individuals.4 In the aging, NK cells may be fewer, secrete perforin with more difficulty, and die faster compared to NK cells in younger people. Many new animal and human studies show that NK cells play a central role in the immune surveillance of transformed cells,5 while evidence suggests that our low NK cell activity may be a risk factor for malignancy or metastases, as well as a negative prognostic indicator.6 In fact, our lifestyles, as well as our environment and food habits, influence human natural killer cells, increasing or decreasing their activity to protect against infection or cancer7; today, we probably have decreasing NK cell activity, which increases the risk of cancer. Cancer patients have very low NK cell activity, about 50-70% decreased activity compared to healthy individuals.
Figure 1. Landscape of the Immune Tumor Microenvironment
Function of NK Cells
NK cells constantly patrol in our blood and lymph in their resting phase; but if infected or cancer cells are detected through the ligand place on the surface of target cells, they become active with cytotoxic properties.
Unlike other immune cells, NK cells require no special instruction to recognize a specific antigen. They have the ability to directly recognize cellular targets without prior sensitization, mediated by a network of inhibitory or activating receptors expressed on the cell surface that control NK cell activation. It is the integration of the activating and inhibitory signals that determine if the NK cell becomes cytotoxic. The use of immunotherapeutic agents to increase activation and decrease inhibitory signaling has the potential to generate NK cells with enhanced tumor-lytic capacity.
NK cells become active in response to immuno-regulatory proteins called cytokines that interact with NK cell receptors. NK cells are regulated by various cytokines such as IL-1, IL-12, IL-15, IL-18, and IL-21 that interact with inhibitory or activating receptors on NK cells and communicate with other cells. For instance, the combination of IL-12 and IL-18 is especially potent to trigger interferon (IFN)-y. The NK cells are converted into lymphokine-activated killer (LAK) cells. These LAK cells propagate, produce cytokines and adhesion molecules to target cells, and increase tumor lysis activity.
NK cells also generate an adaptive immune response by secreting pro-inflammatory cytokines and interferon such as TNFa and IFN-y that activate other immune cells such as macrophage, B-cells, and dendritic cells.8
NK Cell Cytotoxicity
The natural killer cell cytotoxicity can be demonstrated in several related ways. The primary and most important known mechanism when attacking cancer cells is based on the release of cytotoxic granules from their cytoplasm after becoming active in response to cytokines.
First, NK cells attach themselves to receptors on the membrane of cancer cells and inject granules called perforin, which is a membrane-disrupting protein that perforates the target cell membrane and forms pores, creating an aqueous channel that permits the entry of another cytotoxic protease.9 (See Figure 2)
Figure 2. RBAC activating NK cells and attacking cancer cells. We observe a single NK cell attaching itself to 3 cancer cells for destruction.
When the pores are formed, NK cells release and inject, via this channel, granzymes serine proteases,10-11 which cleave caspases 3-7-9 and subsequently induce apoptosis in target cells by degrading protein involved with DNA integrity. This is the main channel utilized by NK cells to destroy cancer cells. One NK cell can kill a cancer cell in five minutes time and repeat this 27 times before dying. It shows the great capacity of this unique cell to kill cancer. As we have already indicated, cancer patients have a low NK cell activity compared to healthy individuals. Both in vitro and in vivo tests confirmed that the number of cytotoxic granules increase with NK cells stimulated by RBAC.
It seems that our lifestyle and diet can also increase the activity of NK cells with a balanced diet that included a variety of vegetables, fruits, meat, and fish being associated with higher levels of perforin and granzymes, efficiently serving as protection against cancer cells.12
Natural Killer Cells and Cytokines
Not only can NK cells target and kill cancer cells through cytotoxic granules, but when activated they have one other interesting indirect targeting mechanism. When activated NK cells release pro-inflammatory cytokines and interferons such as IFN-y and TNFa8 that can cause direct tumor necrosis by inflicting tumor-associated capillary injury but also (and this is important) generate an adaptive immune response by activating other immune cells such as macrophages, T-cells, and dendritic cells.13 The secretion of IFN-y by NK cells plays a key role in the stimulation and maturation of dendritic cells and thus increasing, even more, the killing of cancer cells.14 Also, one other advantageous factor is the fact that IFN-y secreted by the NK cells contributes to inhibiting angiogenesis and blood vessels, a major step required for tumor growth and expansion. Therefore, NK cells seem to have a wide targeting effect besides killing cancer cells directly.
Perforin-Independent Apoptotic Channel
NK cells use another apoptotic weapon channel to kill cancer cells. This is a perforin-independent mechanism using the death receptor ligand. This cytotoxic pathway relies on tumor necrosis factor (TNF) receptor superfamily members.15 The two main TNF receptors used in apoptotic induction are FAS (CD95) and Trail (TNF-related apoptosis-inducing ligand).16 Trail is an apoptotic molecule that interacts with the death receptors Dr4 and Dr5 and activates intracellular apoptosis through cleavage of caspase 8, which in turn can directly activate caspases 3-9. Literature has shown that Trail can kill any cancer or leukemia cell regardless of their degree of malignancy.
Page 1, 2, 3