Link between gut and type 1 diabetes

Scientists have found that targeting micro-organisms in the gut, known as microbiota, could have the potential to prevent type 1 diabetes. University of Queensland researcher Dr. Emma Hamilton-Williams investigated differences in the gut microbiota, comparing those susceptible to type 1diabetes to those protected against the autoimmune disease.

This research has shown there is a genetic component to microbiota and the immune response involved in regulating it, this means that changes in the microbiota in type 1 diabetes occur before symptoms develop, and are not just a side-effect of the disease. Therapies targeting the microbiota could therefore have the potential to help prevent type 1 diabetes in the future.

An immunotherapy targeting T-cells associated with type 1 diabetes resulted in dramatic changes in the gut biology and altered the microbiota in mice models. Genetic susceptibility and change in immune system function led to alterations in the microbiota. The implications are that a person's genetics contribute to an unhealthy microbiota as well as their diet.
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Treating aggressive colon tumor with immunotherapy

Immunotherapy against cancer cells has become a powerful approach to treat cancers such as melanoma and lung cancer. However, to date, most colon tumours appeared to be unresponsive to this kind of therapy. Given this observation, researchers hypothesized that this kind of tumour was simply invisible to the immune system.

A team headed by ICREA researcher Eduard Batlle, at the Institute for Research in Biomedicine (IRB Barcelona), explains that the hormone TGF-beta is responsible for the "blindness" of the immune system to colon cancer cells. The few clinical immunotherapy trials done in patients with the most common subtype of colon cancer were not giving good results.

By inhibiting the activity of TGF-beta, the cells of the immune system infiltrate and recognise the tumour, fight the cancer, and even stop colon tumours from metastasizing to the liver and lung in a preclinical mouse model that mimics the human disease. In addition, and more importantly, the researchers demonstrated that the combination of a TGF-beta inhibitor with available immunotherapies boost the anti-tumour effect, allowing the immune system to efficiently eliminate already established metastases that would otherwise kill the individual in a question of weeks.

Scientist Daniele Tauriello, postdoctoral fellow and first author of the article, induced four of the most common mutations present in advanced human colon tumours in mice. After confirming the similarity of the mouse tumours with those in humans, they built a biobank of tumour organoids3-D mini-tumours and grafted them in a controlled manner in immunocompetent mice.

For studies of the immune system, the tumour has to be of mouse origin. Otherwise, the animal would reject it.This animal model which mimics the main features of metastatic colon cancer in humans, allowed the researchers to examine how cancer cells evade the immune system. Around 40 to 50 percent of colon cancer patients relapse in the form of metastasis, with the tumours reproducing mainly in the liver and lung.

Once advanced stage colon cancer is diagnosed, oncologists do not have access to efficient treatments to cure the patient. This study paves the way for the development of the first immunotherapy treatment for patients with metastatic colon cancer and for those patients with poor prognosis but who have not yet developed metastasis. Oncologists and pharmaceutical companies will soon start clinical assays that combine TGF-beta inhibitors, which are already in clinical use, with immunotherapies.

The researchers are convinced that many colon cancer patients will benefit from this therapeutic strategy. In the same issue of Nature, another study addresses the lack of response of bladder cancer patients to immunotherapy.  It appears that many types of tumour use the same strategy-increasing the expression of TGF-beta in the environment to evade the immune system. Patients with these tumours may also benefit from immunotherapies based on the inhibition of this hormone.
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Roles of bacteria in colon cancer

Patients with an inherited form of colon cancer harbor two bacterial species that lead to development of the disease, and the same species have been found in people who develop a sporadic form of colon cancer, a study led by a Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy research team finds.

A second study by the same researchers shows a possible mechanism behind how one of these species spurs a specific type of immune response, promoting-instead of inhibiting the formation of malignant tumors. Together, these findings could lead to new ways to more effectively screen for and ultimately prevent colon cancer.

The Science findings describe a process in which these bacteria invade the protective mucus layer of the colon and collude to create a microenvironment-complete with nutrients and everything the bacteria need to survive that induces chronic inflammation and subsequent DNA damage that supports tumor formation.

These findings suggest a change in the standard of care for people who carry both types of bacteria. "More frequent colon cancer screening than the currently recommended once every 10 years should be considered," says Drew Pardoll, M.D., Ph.D., director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy. Ultimately, once better understood, administering drugs or vaccines to prevent colonization of the bacteria in the colon, and potentially even probiotics to chase the bugs from the colon, are preventive measures that could be explored to interrupt the cancer-promoting process.

These new findings shows that particular strains of bacteria can invade the colon mucus in some patients who get colon cancer but who have no inherited predisposition for the disease. Unlike most bacteria, which do not make it past the colon's protective mucus layer, these communities of bacteria that invade the mucus form a sticky biofilm right next to the colon epithelial cells that line the colon, where colon cancer usually originates.

About 5 percent of colon cancers are caused by a hereditary syndrome called familial adenomatous polyposis (FAP), in which an inherited mutation launches a series of genetic changes that develop over time and eventually prompt the epithelial cells to turn malignant. However, it was unclear whether ETBF or other bacteria played a role in the progression to colon cancer in FAP patients.

To investigate the relationship between the bacteria-caused biofilms and cancer formation, researchers examined colon tissue removed from six FAP patients. Tests showed patchy sections of biofilms distributed along the colon's length in about 70 percent of the patients. The researchers used gene probes to identify the particular bacterial species and found that the biofilms consisted mainly of two types, Bacteroides fragilis and Escherichia coli, a surprising finding since the colon contains at least 500 different types of bacteria.

Tests on 25 additional colon samples from FAP patients showed that the B. fragilis strain was a subtype, called ETBF, which makes a toxin that triggers certain oncogenic, or cancer-promoting, pathways in colon epithelial cells and causes colon inflammation. The E. coli strain produced a substance called colibactin (synthesized by a set of genes in the bacterial genome called the PKS island), which causes DNA mutations.

FAP is a devastating disease that ultimately results in surgical removal of the colon, a Currently, using colonoscopy to monitor for the formation of precancerous tumors, called polyps, is the standard of care. Using a mouse model of colon cancer, the researchers found that animals whose colons were colonized with just one of these species developed few or no tumors. However, when their colons were colonized with both species simultaneously, they developed many tumors, suggesting a synergy between the two types of bacteria.

An earlier study suggested a unique type of immune response producing an inflammatory protein called IL-17-was key to ETBF-induced tumor formation. In order to prove the importance of IL-17 in the cancer-promoting effects of the bacterial combination, they used a mouse model in which the IL-17 gene was genetically deleted so it could not make IL-17, and colonized the mice with both ETBF and PKS+E. coli. Unlike animals that readily made IL-17, the genetically altered mice didn't form colon tumors, confirming the importance of this protein in bacterial-driven colon cancer.

However, in addition to IL-17, the studies showed that ETBF digested the mucus layer, enabling the PKS+ E. coli to adhere in larger numbers to the colon mucosa where together the bacteria induced increased DNA damage, a step preceding the gene mutations that underlie colon tumor formation. The complementary findings in Cell Host & Microbe demonstrate how ETBF's toxin prompts colon cancer to develop. Using a different mouse model of colon cancer, the researchers colonized the animals' colons with ETBF and then performed a series of tests to monitor the resulting cellular and molecular changes.

Their results revealed that ETBF's toxin spurs a cascade of events that promote colon inflammation that feeds back to act on the colon epithelial cells. First, the toxin triggers colon immune cells to produce IL-17. This inflammatory molecule then acts directly on the colon epithelial cells to trigger activation of a protein complex involved in promoting further inflammation, known as NFkappaB. NFkappaB in turn induces the colon epithelial cells to produce several signaling molecules that recruit more immune cells, called myeloid cells, to the colon.

These immune cells are involved in the inflammatory response and are known to support tumor growth. This process culminates in tumors forming in the colon. Additional experiments showed that a protein known as STAT3, which was previously shown to play a role in regulating cancer and inflammatory genes, is also necessary for tumor formation.
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Therapeutic for pancreatic cancer

In most pancreatic cancer patients, the diagnosis occurs when the disease is already advanced, and currently, there is no effective treatment. A group of researchers from the Spanish National Cancer Research Centre (CNIO) may have found a new therapeutic approach.

One of the characteristics of pancreatic cancer is that the tumour cells are embedded in the stroma, which represents 90 percent of the tumour mass and which seems to form a barrier (physical and chemical) hindering treatment with inhibitors, chemotherapy and immunotherapy.

Researchers focused their work on identifying a stromal cell population that fosters tumour growth, to later discover why they have this capacity and reverse it. The strategy to achieve the latter is innovative, because instead of eliminating these stromal cells which help the tumour, the objective has been their selective reprogramming. The researchers focused on a subpopulation of fibroblasts known to play a role in inflammation, because inflammation fosters tumour growth.

Their analysis revealed that the Saa3 gene is responsible for CAFs helping tumour cells to progress. When the researchers eliminated the expression of this gene in the CAFs, these cells behaved like normal fibroblasts, losing the ability to accelerate tumour cell progression. Researchers had managed to "reprogramme" these cells, which had been stripped of their pro-tumour properties.

In human samples of pancreatic cancer, the researchers have identified the same population of pro- tumour fibroblasts, and have observed that when the SAA1 gene (the human version of Saa3) is overexpressed, the prognosis for the patients is far worse.
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Reovirus could treat brain tumours

A virus injected directly into the bloodstream could be used to treat people with aggressive brain tumours, Scientists have found that the naturally occurring virus could act as an effective immunotherapy in patients with brain cancer or other cancers that have spread to the brain. They showed that a type of virus called reovirus could cross the blood-brain barrier to reach tumours, where it replicates and kills the cancer cells.

They also found that the virus was able to 'switch-on' the body's own defense systems to attack the cancer. The study authors, from the University of Leeds and The Institute of Cancer Research in London, believe reovirus therapy could be used in conjunction with other cancer therapies to make them more potent - and a clinical trial is currently underway. Because the virus infects cancer cells and leaves healthy cells alone, patients receiving the treatment reported only mild flu-like side effects.

Scientists thought it was unlikely that the virus would be able to pass from the blood into the brain because of the blood-brain barrier, a protective membrane around the brain. That would have meant that the only way they could get the virus into the brain was to inject it directly into the brain - which is challenging, would not be suitable for all patients, and cannot be regularly repeated. But the research demonstrated that the virus could be administered through a single-dose intravenous drip.

Nine patients took part in the study, they had cancers that had either spread to the brain from other parts of the body or were fast-growing gliomas, a type of brain cancer that is difficult to treat, and has a poor prognosis. All the patients were due to have the tumours removed surgically. But in the days before the surgeons operated, the patients were given the virus drip.

Once the tumours were removed, samples were taken and analysed for signs that the virus had been able to reach the cancer, sometimes deep within the brain. In all nine patients, there was evidence that the virus had reached its target. The researchers also found that the presence of reovirus stimulated the body's own immune system, with white blood cells or 'killer' T-cells being attracted to the tumour site to attack the cancer.

Tissue samples from patients who had surgery but not the virus therapy served as a control. When compared with the control samples, the tissue taken from the people who had received the reovirus had higher levels of interferons, proteins that 'switch-on' the body's immune system. According to Dr Adel Samson, co-lead author and medical oncologist at the Leeds Institute of Cancer and Pathology, at the University of Leeds, "This is the first time it has been shown that a therapeutic virus is able to pass through the brain-blood barrier, and that opens up the possibility this type of immunotherapy could be used to treat more people with aggressive brain cancers.

Human immune systems aren't very good at detecting cancers, because cancer cells look like human body's own cells, and partly because cancers are good at telling immune cells to turn a blind eye. But the immune system is very good at seeing viruses. In the study, they were able to show that reovirus could infect cancer cells in the brain. And, importantly, brain tumours infected with reovirus became much more visible to the immune system.

Although the earlier trial demonstrated that the reovirus was reaching the cancer cells after just a single dose, doctors have decided to give it repeatedly to patients because of the way it 'kick starts' the body's own defences. The presence of cancer in the brain dampens the body's own immune  system. The presence of the reovirus counteracts this and stimulates the defence system into action. Additional effect of the virus on enhancing the body's immune response to the tumour will increase the amount of tumour cells that are killed by the standard treatment, radiotherapy and chemotherapy.
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Gene therapy can destroy HIV infected cells

Through gene therapy, researchers engineered blood-forming stem cells (hematopoietic stem/progenitor cells, or HSPCs) to carry chimeric antigen receptor (CAR) genes to make cells that can detect and destroy HIV-infected cells. These engineered cells not only destroyed the infected cells, they persisted for more than two years, suggesting the potential to create long-term immunity from the virus that causes AIDS.

Antiviral drugs can suppress the amount of HIV in the body to nearly undetectable levels, but only an effective immune response can eradicate the virus. Researchers have been seeking a way to improve the body's ability to combat the virus by engineering blood-forming stem cells to specifically target and kill HIV-infected cells for the life of the individual.

 Although chimeric antigen receptor (CAR) T-cells have emerged as a powerful immunotherapy for various forms of cancer -- and show promise in treating HIV-1 infection -- the therapy may not impart long-lasting immunity. Researchers, physicians and patients need T cell-based products that can respond to malignant or infected cells that may reappear months or years after treatment.

Because HIV uses CD4 to infect cells, the researchers used a CAR molecule that hijacks the essential interaction between HIV and the cell surface molecule CD4 to make stem cell-derived T-cells target infected cells. When the CD4 on the CAR molecule binds to HIV, other regions of the CAR molecule signal the cell to become activated and kill the HIV infected cell.

The researchers found that, in test animals, modification of the blood-forming stem cells resulted in more than two years of stable production of CAR-expressing cells without any adverse effects. In addition, these cells were widely distributed throughout the lymphoid tissues and gastrointestinal tract, which are major anatomic sites for HIV replication and persistence in infected people. Most important, engineered CAR T-cells showed efficacy in attacking and killing HIV-infected cells.
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DNA sensor and cancer immunotherapy

Tumors stressed by cancer immunotherapy release their mitochondrial DNA into the closer immune cells, causing a host alert system. The chemical alert through the molecule cGAS is an important immune-system sensor for DNA that is in the interior of cells, the cytosol, where DNA should not exist. 

 cGAS connected the innate immune system, which senses initial threats; and the adaptive immune system, which amplifies the anti-tumor response after getting the alert from the innate immune system. The adaptive system battles recurring threats from pathogens. Checkpoints are molecular barriers that cancer cells produce to make themselves undetectable to the immune system. The plan of immunotherapy is to make the cancers detectable.

Current immune checkpoint blockade therapy has been life-extending for many people. The drug targets CD47, a cell surface protein highly expressed in some tumor cells. CD47 signal to block immune cells from killing the cancer cells. cGAS as an innate immune sensor of DNA led to speculation that inhibition of cytosolic DNA sensing could represent a strategy tumor cells used to evade the immune system.

CD47 is found in every cell of the body, and it has long been known that many kinds of cancer cells produce higher amounts of CD47 than healthy cells. CD47 signal helps cancer cells evade detection from the immune system's killer T-cells.

The higher the levels of CD47 found in tumors, the poorer the prognosis for many cancers. Using mouse cells,
the researchers discovered that when cancer cells are stressed by an experimental anti-CD47 immunotherapy, it leaks DNA into nearby dendritic cells, which present antigens to killer T-cells and are considered a bridge between the innate and adaptive immune systems.

 The DNA sensor cGAS sounds the alarm inside those dendritic cells, setting off a signaling cascade that alerts the
immune system and unleashes the cancer-killing T-cells. cGAS is essential for cancer immunotherapy by immune checkpoint blockade. Activating DNA comes from the mitochondria of the cancer cells. Tumor-originated mtDNA was recognized by the DNA sensor cGAS in dendritic cells during anti-CD47 treatment.

 cGAS-STING-IRF3 signaling pathway plays a critical role to drive robust innate and adaptive immune response upon anti-CD47 therapy. Understanding this mechanism of anti-CD47 therapy may make it possible to design new combination strategies to improve current immune checkpoint blockade therapies by modulating the innate sensing of mtDNA.
       

Pioneering test can predict future of breast cancer

A pioneering test could be used to predict whether breast cancer will return. Patients with clustered immune cells, called hotspot were 25 per cent more likely to relapse within 10 years.

The probability of the cancer returning within five years was 23 per cent higher in women with the hotspot. The new method gives doctors the opportunity to provide better preventative drugs to prevent the cancer.

The automated computer tool made an assessment of the risk of relapse based on how cells are organised spatially.
People with dispersed immune cells have better chance of fending off the cancer.

Pioneering test also predict patients that will respond to immunotherapy.
The immune system has a key role to play in how breast cancer responds to hormone treatment.

Measuring the immune response to cancer could be important in the future to identify patients who could benefit from immunotherapy. The immune tool could be added to existing prognostic tests to identify women that are at high risk of their breast cancer coming back.
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When allergies are out of control

Allergens are foreign substances that cause an allergic reaction in the body, allergy symptoms occur when immune system overreacts to something that is harmless but triggers a reaction in the blood.

Food, skin, dust, insect, pet, pollen and drug are the common types of allergies.
In allergic individuals, the body recognizes the foreign substance, and the allergic part of the immune system generates a response.

Avoiding exposure to things you are allergic to is the best way to control the symptoms. Immunotherapy may be an option for people with severe and persistent allergies who are unable to control their symptoms.

The treatment involves being given occasional small doses of the allergen; either as an injection, or as drops or tablets. The treatment will strengthen the body to get used to the allergen so it doesn't react to it so severely again.
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Autoimmunity contributes to Parkinson's disease

 Autoimmunity  is when the immune system attacks the body's own tissues. Parkinson's disease is neurodegenerative movement disorder.
Malfunctioning immune system contributes to Parkinson's disease.

Two fragments of alpha-synuclein, a protein that accumulates in the brain cells of Parkinson's disease patients can activate the T cells involved in autoimmune attacks.

Dopamine neurons that are affected by Parkinson's disease are vulnerable because they have proteins on the cell surface that help the immune system recognize foreign substances.

 Researchers examined blood samples from 67 Parkinson's disease patients and 36 healthy controls to fragments of alpha-synuclein and other proteins found in neurons.

 The immune response was associated with a common form of a gene found in the immune system, which may explain why many people with Parkinson's disease carry this gene variant.

 Immunotherapy can be used to increase the immune system's tolerance for alpha-synuclein, which could help to prevent worst condition of Parkinson's disease.

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Treatment and prevention of cancer

Treatment of cancer depends on the type and stage of the cancer. Age and health status of the patients will also dictate the treatment.

Common cancer treatment are: surgery,
radiation, chemotherapy, immunotherapy, hormone therapy or gene therapy.

Cancer can be prevented by eating healthy diet. Eating foods that are low in fat, rich in fresh fruits, vegetables and whole grains can reduce risk of having cancer.

Some vaccines have been associated with prevention of some cancers. For example, vaccination for the human papillomavirus prevents cervical cancer. Hepatitis B vaccines prevents
hepatitis B virus, which can cause cancer of the liver.

Breast self-examination, mammograms, testicular self-examination, and Pap smears are common screening methods for different cancers prevention.

You can prevent cancer by, being physically active, eating a healthy diet, controlling cholesterol, managing blood pressure, reducing blood sugar and not smoking.

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Nivolumab drug can kill abestos cancer

Asbestos was once a popular building material, but it was discovered that exposure to it causes mesothelioma cancer.

Mesothelioma affects the lungs, and the lining surrounding the lower digestive tract. Symptoms are chest or lower back pain shortness of breath  and excessive sweating.

Nivolumab is effective for treating melanoma and kidney cancer it blocks PD-1 on the surface of T-cells, then activate immune system cells to hunt down and kill cancer cells.

It’s an example of immunotherapy, a type of cancer treatment which boosts the body’s natural defences in order to fight cancer.

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Nanoparticle vaccine can kill different types of cancer

Researchers at UT Medical Center has developed nanoparticle vaccine Immunotherapy that can kill different types of cancer.

Nanoparticle vaccines provide minuscule particles that activate the immune system to mount an immune response.

Vaccines normally use immune cells to get tumor antigens where it is located and move to the lymphoid organs for T cell activation.

Nanoparticle vaccines can go directly to the lymph nodes to activate the particular tumor immune responses.

Researchers tested many tumor models in mice like: colorectal cancer, melanoma, cancers of the cervix, head, neck and anogenital region.

Nanoparticle hinders tumor growth and increase the lifestyle of mice, this will be a suitable vaccine for patients with multiple cancer.

How to target blood vessels to improve cancer Immunotherapy

The aims of cancer immunotherapy is to empower patients immune system T cells to recognize and attack cancer.

Tumors used several methods to fight back immune system attack, like producing blood vessels that hinder arrival of T cells.

Scientists are now reprogramming the tumor blood vessels to treat different types of cancers.

Tumor blood vessels provide oxygen and nutrients to the growing cancer cells,  scientists  used AZV to block the actions of two proteins: VEGFA and ANGPTZ to starve the tumor.

AzV regress and normalized the tumor blood vessels and facilitated the arrival of activated T cells.

Anti-angiogenic drugs like ANGPTZ inhibitors have strong effect on tumor and initiative anti-tumor immune responses.

The link between blood vessels and Immune system

Researchers at Baylor College of Medicine have discovered that tumor blood vessels and immune system influences each other's roles.

There are different therapies for cancer, some therapies stop tumour growth by controlling the blood vessels that protects the tumor mass, others work on the immune system and trying to destroy the tumor.

Anti blood vessel therapies and immunotherapies have been used in treatment of cancer; immunotherapy has record great success in some cancer treatment like melanoma, but some patients are not responding to these therapies.

Researchers suggest consideration of vascular structure of the tumor and the presence of immune cells and their activities. Anti-cancer therapies toward the blood vessels is influencing the anti-tumor immune response and the other way round. Combining the therapies may produce a better result.

Patients immune system and cancer Immunotherapy

Researchers discovered that higher levels of tumor-associate immune cells TAICs expressing programmed death-ligand 1 PD-L1 were linked with longer complete survival and response to drugs.

Patients with higher levels of circulating CD8 and lower level of regulatory T cells were associated with better response to the treatments based on the blood samples before Immunotherapy.

This shows that immune cells in the microenvironments close to the tumor could determine how cancer patients will respond to treatment.

According to Dr Robert Ferris, determining the nature of cells and how treatment affects them will improve the effectiveness of therapies.

Mesothelioma is getting better with immunotherapy drug

Mesothelioma is a type of cancer that develops in the lining of the lungs and chest wall, it is causes by inhalation of asbestos fibre.

It is difficult to detect the cancer at early stage because their is no symptoms until it reach an advanced stage.

An immunotherapy drug,
Pembrolizumab seems to be effective in the treatment of mesothelioma.

First-line therapy is the standard treatment for mesothelioma, according to Dr.Evan Alley, researchers have studied different drugs but have not seen positive results.

Pembrolizumab is a checkpoint inhibitor, it is designed to fight cancer by defeating process that cancer cells use to avoid being destroyed by the immune system.

Common adverse effect of the drug are: dry mouth, nausea, fatigue, and loss of appetite.

Facts about Melanoma

1. Melanoma is a cancer that begins in the melanocytes.

2. Ultraviolet radiation increases the risk of melanoma

3. Over exposure to the sun can damage DNA and leads to melanoma.

4. It accounts for 5% of all skin cancer and it's the most dangerous types of skin cancer.

5.  Melanoma can develop in any part of the skin.

6.  Having lots of moles on the skin can cause melanoma.

7.  One of the common symptoms of melanoma is sore that do not heal.

8.  Red raspberries fruits  and green tea may prevent it.

9.  Daily intake of raw garlic can prevent melanoma

10.  Common treatments include:
• Chemotherapy
• Immunotherapy
• Surgery
• Targeted therapy