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Cancer immunology is the study of interactions between the immune system and cancer cells (also called tumors or malignancies). It is also a growing field of research that aims to discover innovative cancer immunotherapies to treat and retard progression of this disease. The immune response, including the recognition of cancer-specific antigens is of particular interest in this field as knowledge gained drives the development of new vaccines and antibody therapies. For instance in 2007, Ohtani published a paper finding tumour infiltrating lymphocytes to be quite significant in human colorectal cancer.[1] The host was given a better chance at survival if the cancer tissue showed infiltration of inflammatory cells, in particular lymphocytic reactions. The results yielded suggest some extent of anti-tumour immunity is present in colorectal cancers in humans.

Preoperative treatment with a non-steroidal anti-inflammatory drug (NSAID) increases tumor tissue infiltration of seemingly activated immune cells in colorectal cancer. Lönnroth C, Andersson M, Arvidsson A, Nordgren S, Brevinge H, Lagerstedt K, Lundholm K. Cancer Immun. 2008 Feb 29;8:5. PMID: 18307280 MHC II protein (HLA-DP, -DQ, -DR) levels and infiltration by CD4+ T-helper cells of tumor stroma increased upon NSAID treatment, while CD8+ cytotoxic T-lymphocytes increased in both tumor stroma and epithelium. Molecules associated with immunosuppressive T regulatory cells (FOXP3, IL-10) were significantly decreased in indomethacin-exposed tumors. Standard oral administration of NSAID three days preoperatively was enough to increase tumor infiltration by seemingly activated immune cells. These findings agree with previous information that high pr

Researchers at McGill University and the University of Pennsylvania have discovered that a widely used anti-diabetic drug can boost the immune system and increase the potency of vaccines and cancer treatments. Their findings will be published June 3 in the journal Nature. The discovery was made by Dr. Russell Jones, an assistant professor at McGill's Goodman Cancer Centre and the Department of Physiology, Faculty of Medicine, Yongwon Choi, PhD, professor of pathology and laboratory medicine, and postdoctoral fellow Erika Pearce, PhD, of the University of Pennsylvania. They discovered that the widely prescribed diabetes treatment metformin increases the efficiency of the immune system's T-cells, which in turn makes cancer and virus-fighting vaccines more effective.

T-helper/T-regulator lymphocyte ratio as a new immunobiological index to quantify the anticancer immune status in cancer patients. Brivio F, Fumagalli L, Parolini D, Messina G, Rovelli F, Rescaldani R, Vigore L, Vezzo R, Vaghi M, Di Bella S, Lissoni P. In Vivo. 2008 Sep-Oct;22(5):647-50. PMID: 18853761 RESULTS: The mean TH/TR ratio observed in patients with metasytases was significantly lower with respect to that found in both patients without metastases and controls. On the contrary, the absolute mean number of T-reg cells was higher in patients with metastases than in those without, but the difference was not statistically significant. CONCLUSION: The evaluation of T-reg cells in terms of their proportion with respect to T-helper cell total number seems to be more appropriate than the simple measurement of their absolute count, in order to quantify cancer-related immunosuppression. Thus, the TH/TR ratio could represent a useful biological marker to explore the immune status of cancer patients.

"Língzhī (traditional Chinese: 靈芝; simplified Chinese: 灵芝; Japanese: reishi; Korean: yeongji, hangul: 영지) is the name for one form of the mushroom Ganoderma lucidum, and its close relative Ganoderma tsugae. Ganoderma lucidum enjoys special veneration in Asia, where it has been used as a medicinal mushroom in traditional Chinese medicine for more than 4,000 years, making it one of the oldest mushrooms known to have been used in medicine. Lingzhi may possess anti-tumor, immunomodulatory and immunotherapeutic activities, supported by studies on polysaccharides, terpenes, and other bioactive compounds isolated from fruiting bodies and mycelia of this fungus (reviewed by R. R. Paterson[4] and Lindequist et al.[7]). It has also been found to inhibit platelet aggregation, and to lower blood pressure (via inhibition of angiotensin-converting enzyme[8]), cholesterol and blood sugar.[9] Laboratory studies have shown anti-neoplastic effects of fungal extracts or isolated compounds against some types of cancer. In an animal model, Ganoderma has been reported to prevent cancer metastasis,[10] with potency comparable to Lentinan from Shiitake mushrooms.[11] The mechanisms by which G. lucidum may affect cancer are unknown and they may target different stages of cancer development: inhibition of angiogenesis (formation of new, tumor-induced blood vessels, created to supply nutrients to the tumor) mediated by cytokines, cytoxicity, inhibiting migration of the cancer cells and metastasis, and inducing and enhancing apoptosis of tumor cells

Coriolus versicolor is a mushroom of the Basidiomycetes class. It was used initially in Traditional Chinese medicine as a tonic, but recent studies suggest that it has immunostimulant and anti-tumor properties. Polysaccharide-K (PSK), a proprietary product derived from Coriolus, was developed for cancer treatment in Japan. When used as an adjuvant, PSK appears to improve survival rates in patients with gastric (1) (2) and colorectal (3) (4) (5) cancers. Other Coriolus extracts, such as polysaccharide-peptide (PSP) and VPS, are available as dietary supplements. When used in conjunction with chemotherapy, PSP may benefit patients with advanced non-small cell lung cancer (7). Other clinical studies using Coriolus extract alone or in combination with other botanicals also suggest positive immunomodulatory effects (8) (9). However, studies on breast cancer (10), hepatocellular carcinoma (11), and leukemia (12) produced mixed results. A hot water extract of Coriolus, VPS, was found to enhance development of large intestinal tumors in mice (21). Coriolus extracts are generally well tolerated but minor adverse effects have been reported. Many over-the-counter Coriolus products are not standardized, making it difficult to compare potency between brands. It is also unclear if PSK, PSP and other Coriolus extracts have comparable effects.

Interleukin 2-mediated conversion of ovarian cancer-associated CD4+ regulatory T cells into proinflammatory interleukin 17-producing helper T cells. Leveque L, Deknuydt F, Bioley G, Old LJ, Matsuzaki J, Odunsi K, Ayyoub M, Valmori D. J Immunother. 2009 Feb-Mar;32(2):101-8. PMID: 19238008 doi: 10.1097/CJI.0b013e318195b59e Thus, although the impact of TH17 cells on the evolution of EOC remains to be established, our data suggest that local IL-2 treatment in ovarian cancer may result in the conversion of tumor-associated Treg into TH17 cells, relieve Treg-mediated suppression, and contribute to enhance antitumor immunity.

Derived from the cap and stem of the mushroom, Reishi mushroom is used as an immune stimulant by patients with HIV or cancer. The active constituents are thought to include both beta-glucan polysaccharides and triterpenes (1). Extracts of Reishi can stimulate macrophages and alter the levels of TNF and interleukins (2) (3) (4) (5). Reishi also inhibited platelet aggregation (11) (12) and improved lower urinary tract symptoms (LUTS) in men (9) (10). Studies done in rats have shown that Reishi extract may alleviate chemotherapy-induced nausea (13). In clinical studies, Reishi increased plasma antioxidant capacity (6) (7)and enhanced immune responses in advance-stage cancer patients (8).

Multiple roles for CD4+ T cells in anti-tumor immune responses. Kennedy R, Celis E. Immunol Rev. 2008 Apr;222:129-44. Review. PMID: 18363998 DOI: 10.1111/j.1600-065X.2008.00616.x

"For years, it's been the perfect excuse for secret admirers to steal a kiss with the object of their desire. But research suggests mistletoe could do much more than just ignite Christmas passions. Scientists have found an extract of the plant could help to fight bowel cancer, which affects 37,500 a year in the UK. Patients who had the mistletoe treatment regularly injected into their blood had fewer side-effects from toxic chemotherapy and radiotherapy and survived longer than those who did not. The extract is thought to help the body's immune system fight tumours and speed up the disposal of toxic 'debris' left by chemotherapy. Researchers led by Professor Kurt Zanker from the German Institute of Immunology and Experimental Oncology, concluded: 'The results suggest convincing evidence that there is a significant benefit from treatment with mistletoe extract.' The scientists treated 429 cancer patients with the mistletoe jab and compared them with 375 receiving conventional care. The results, published in the journal of The Society For Integrative Oncology, showed only 19 per cent of those in the mistletoe group suffered side-effects from toxic treatments, compared to 48 per cent in the other group. They were also 32 per cent more likely to still be alive five years after starting therapy."

In vitro and in vivo anti-tumor effects of Astragalus membranaceus. Cho WC, Leung KN. Cancer Lett. 2007 Jul 8;252(1):43-54. Epub 2007 Jan 16. PMID: 17223259 doi:10.1016/j.canlet.2006.12.001

Derived from the bulb or clove of the plant. Garlic is used as a spice and to treat hyperlipidemia, hypertension, atherosclerosis, cancer, and infections. Processing can have a substantial effect on the chemical content in garlic; the volatile oil components are sensitive to heat and certain enzymes are acid-labile. Several oral garlic formulations are available, and clinical studies have addressed a variety of the proposed claims. Placebo-controlled trials on the cholesterol lowering effect of garlic yielded mixed results (16) (17) (18) (21) (22) (26). Studies evaluating the antithrombotic effects repeatedly have shown modest reduction in platelet aggregation, but varying levels of fibrinolytic activity. Research shows mixed effects with regard to reductions in blood glucose, blood pressure, or risk of cardiovascular disease (23). Frequently reported adverse events include bad breath, headache, fatigue, GI upset, diarrhea, sweating, and possible hypoglycemia (9). Because garlic is known to decrease platelet aggregation and potentially elevate the INR, it should not be used with anticoagulants or in patients with platelet dysfunction (15). Garlic appears to induce cytochrome p450 3A4 and may enhance metabolism of many medications (e.g. cyclosporin and saquinavir) (12). An analysis of several case-control studies in Europe suggests an inverse association between garlic consumption and risk of common cancers (25).

Attached please find the final draft of Dr. Kenyon's non-controlled observational study on the use of Coriolus versicolor (non-extracted) in 30 solid tumour cancer patients. The final report will be published in the February edition of Mycology News 7. The patients were Stage III and Stage IV patients in which chemotherapy and radiotherapy were not considered successful. Below please find a synopsis of patient type.

beta-glucan A polysaccharide isolated from the cell walls of bacteria, plants, and fungi with immunostimulant and antineoplastic activities. In a solubilized form, beta-glucan binds to a lectin site within complement receptor 3 (CR3) on leukocytes, priming the receptor to trigger cytotoxic degranulation of leukocytes when leukocyte CR3 binds to complement 3 (iC3b)-coated tumors. Thus, the attachment of beta-glucan to CR3 of circulating leukocytes simulates leukocytes to kill iC3b-coated tumor cells in the same way as they kill iC3b-coated yeast. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Derived from the cap and stem of the mushroom. The active constituent is thought to be a beta-glucan polysaccharide. The whole mushroom is used primarily as a dietary element, but extracts and supplements are sold as immune stimulants for patients with HIV or cancer. While no adverse effects have been reported, some studies reveal a hypoglycemic effect following administration of maitake extract (9) (12). Maitake was shown to enhance bone marrow colony formation, reduce doxorubicin toxicity in vitro (11), and to inhibit tumor metastasis

Shiitake mushroom, native to East Asia, is cultivated worldwide for its purported health benefits. The fresh and dried forms of the mushroom are commonly used in East Asian cooking. It is also valued as an anticancer agent. Lentinan (1,3 Beta-D-glucan), a polysaccharide isolated from Shiitake, has been well studied and is thought responsible for its beneficial effects. It was shown to have anticancer effects in colon cancer cells (1), which may be due to its ability to suppress cytochrome P450 1A enzymes that are known to metabolize pro-carcinogens to active forms

A proprietary extract prepared from co-cultured mycelia of several species of Basidiomycete mushrooms, including shiitake (Lentinus edodes), active hexose correlated compound (AHCC) is extracted from mushrooms using hot water following an enzyme pretreatment, but specific mushroom source and preparation details have not been fully disclosed. Patients use this to prevent and treat cancer. Animal studies suggest that AHCC has antioxidant effects and may protect against disorders induced by oxidative stress (1) and may also enhance resistance against bacterial (2) (7)and viral infections (3). In healthy humans, AHCC increased dendritic cell number and function (4) In vitro and animal studies show that AHCC exhibits some anticancer activities, but the results of these studies are vague

If you're from Japan, you're probably wondering why I've listed PSK under alternative therapies. In Japan, PSK is an approved anti-cancer drug with 20 years of research behind it. PSK sales in Japan account for hundreds of millions dollars worth of sales each year. But in the US, PSK is little known, is not used by mainstream doctors, and until recently nothing like it was readily available. Now a nutritional supplement designed to be identical to PSK is available in the US, but very few mainstream doctors, and actually not many alternative practitioners are aware of it. So in the US, PSK has the status of a little known nutritional supplement or alternative therapy. Which is too bad in light of its proven benefits, easy administration, and lack of toxicity. Before I start sounding too much more like an advertisement, let me confess. I really am excited about it, but I have no financial interest in it; I'm not selling it.

Coriolus versicolor extracts: relevance in cancer management M. Szeto, BSC RD Curr Oncol. 2008 April; 15(2): 79.