Uncover immune traitors: the Tregs issue | immunotherapy


	Sunday, 05 September, 2010

Science book

Cancer evolution is an example of competitive evolution. It is a warning that competition (darwinian evolution) is not the way to further evolution. Understand this for the sake of our planet and ourselves...

As a book on cancer evolution, the selfish cell deals with innovative concepts in evolutionary biology. Additionally, new ideas on cancer treatments are forwarded to researchers.

immunotherapy

CRM197 a new immunotherapy for cancer

dendritic_cells

Many years ago, diphtheria toxin (DT) showed antitumor activity in mice and in humans, but it was unclear whether this depended on the toxicity of the molecule only or on its strong inflammatory-immunological property as well. (Buzzi S., Cancer Res. 1982 May;42(5):2054-8). The same researchers, to deal with this open question, planned to treat a group of cancer patients with cross-reacting material 197 (CRM197).

Gc-maf cancer immunotherapy

...The once-weekly injection of minute amounts of Gc-MAF, just 100 nanograms (billionths of a gram), activates macrophages and allows the immune system to pursue cancer cells with vigor, sufficient to produce total long-term cures in humans..."

A report on the creation of a virus obtained genetically modifying a common adenovirus which could constitute a therapy against cancer has appeared recently in the scientific news. This virus would selectively infect cancer cells and force them to express a protein which calls for the intervention of macrophages, additionally stimulating them to multiply. This strategy would therefore help the body mounting a strong immune response against cancer cells.

Cancer immunity trick discovered

Cancer can spread only after having won the fight against the immune system. In the years scientists have discovered a number of strategies put in place by cancer cells to sneak out of the control of the immune system or even to counterfight it. Macrophages, a fundamental arm of immunity, should be put off for cancer affirmation.

They are key determinants in autoimmunity but have been indicated to play a crucial role in cancer immune-evasion (Franzke A, Hunger JK, Dittmar KE, Ganser A, Buer J Regulatory T-cells in the control of immunological diseases. Ann Hematol. 2006 Nov;85(11):747-58. Epub 2006 Jul 27). Increasing evidences support the existence of elevated numbers of these regulatory Treg cells in solid tumors and hematological malignancies.

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Uncover immune traitors: the Tregs issue

Worldwide research in immunology and oncology is recently addressing fundamental aspects of the role of the immune system in tumor development. It is commonly intended the issue needs to be elucidated for its knowledge most probably holds the key for more effective cancer therapies. Among various components of the immune system, suppressive T cells (recently come to be called T regulatory cells of Tregs) are under extensive scrutiny. Tregs appear to have a central role in establishing and maintaining peripheral tolerance and immune homeostasis by exerting suppressive activities on cells of the adaptive and innate immune system.

Although the increase of Treg cells seems to be a characteristic feature of most tumors, little is known about the molecular and cellular mechanisms responsible for the increase and maintenance of elevated levels of Treg cells in cancer. In humans, early studies have been mainly focused on CD4+CD25+ Treg cells, lacking interrogation of more specific markers such as FOXP3 expression, and possibly others.

The discovery of additional molecular markers of cancer-specific Tregs is considered of paramount importance both to support the development of knowledge in the field of immunology or to develop effective anti-cancer treatments targeted toward cancer specific Tregs. A similar approach could be devoid of auto-immune reactions that could be elicited by non selective Tregs elimination strategies.(Beyer M, Schultze JL.Regulatory T cells in cancer. Blood. 2006 Aug 1;108(3):804-11)

Among many potential markers, ion-channels related signatures could already be tentatively indicated. Ion channels are a class of membrane proteins very important for immune cell function and they are often over-expressed and abnormally modulated in cancer microenvironments. It is highly probable that ion channels related signatures could hold memories of an exposition of the immune cells to the tumor microenvironment.( Conti M. Targeting K+ channels for cancer therapy. J Exp Ther Oncol. 2004 Jul;4(2):161-6.)

A specific classification of lymphocytes produced by means of these markers could be an unseful diagnostic tool in a variety of human diseases ranging from auto-immunity related pathologies to graft-versus-host reaction for organ and blood transplantation (Tang Q, Bluestone JA. Regulatory T-cell physiology and application to treat autoimmunity. Immunol Rev. 2006 Aug;212:217-37).

the DCA site

Tumor cells often preferentially use glycolysis to generate adenosine triphosphate (ATP), even in the presence of oxygen, a phenomenon known as aerobic glycolysis, or the "Warburg effect. DCA treatment appears to restore and to boost mitochondrial respiration in cancer cells, consequently causing cancer cell selective killing by a kind of "self-burning" effect.

Reform the FDA

Science constantly discovers new health treatments which are not made available to people because of money reasons. It is time to stand up against these fraud that prevents people getting treatments they need to survive. Read to understand and join action.

cell energy therapy

Leukemia cells metabolize fat to avoid cell death

Leukemia cells, like most cancers, are addicted to glucose to generate their energy, but new research shows that these cells also rely on fatty acid metabolism to grow and to evade cell death.

dca and sugar

DCA promoters recommend taking caffeine and extra thiamine (vitamin B1), hoping that this will help the DCA work better and reduce potential risks of nerve damage. In a survey conducted by the DCA site (www.thedcasite.com) a certain number of heavy tea or coffee drinkers observed astounding responses, even remissions. Here we propose that it could be the sugar contained in those drinks to have helped the DCA mote than, or maybe instead of, caffeine or theophylline.

The DCA therapy

apoptosis

In the review paper "Dichloroacetate (DCA) as a potent..." appeared in the Online first session, in September issue of BJP, Prof. Michelakis most interestingly underlines the importance of targeting the peculiar "aerobic glycolytic" metabolic status of tumors. He suggests that the "Warburg effect", as the phenomenon is more commonly known in the literature, can be modulated by unlocking a mitochondrial impairment in cancer cells and that this could be a very promising strategy to fight cancer.

Can metformin boost DCA?

By itself, metformin was ineffective in treating tumors. In a one-two punch, metformin reduced tumors faster and prolonged remission in mice longer than chemotherapy alone, apparently by targeting cancer stem cells, report Harvard Medical School researchers in the Sept. 14 advance online Cancer Research.

cancer energetic signature

In the last issue of Translational Oncology (2009, 2, pp. 138-145) a report appeared confirming that cellular bioenergetics is a central issue of investigation in cancer biology.

ukrain or oxamate after dca

DCA is in clinical trials and results are expected with great interest. Meanwhile stories can be heard from people, even read on the internet, that tell us that they or their relatives have benefited from using DCA against cancer expecially when combining it with other treatments.

green tea synergize with dca

Recently patients, writing on the DCA site, have reported that adding green tea extracts to their DCA experimental anticancer regimen gave them benefits in term of cure efficacy.