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Health & Medicine for Senior Citizens

Promising new approach for harnessing the immune system to fight cancer released today

St. Jude researchers get immune system to shrink melanoma cancer in mice without autoimmune reaction

Aug. 4, 2013 – Researchers announced today the discovery of a way to target the immune system to shrink or eliminate tumors in mice without causing dangerous autoimmune problems that are often associated with current cancer treatments. They say it was particularly dramatic in a mouse model of human melanoma cancer and shows evidence it may operate in humans.

The report by scientists at St. Jude Children’s Research Hospital published their study in the advance online edition of Nature.

The findings provide a new target for ongoing efforts to develop immunotherapies to harness the immune system to fight cancer and other diseases.

The work focused on white blood cells called regulatory T cells. These specialized cells serve as the immune system’s police force, working to control inflammation and guard against autoimmune and inflammatory disease. Regulatory T cells can, however, interfere with the immune system’s ability to fight cancer.

In this study, investigators identified a mechanism that boosts the ability of regulatory T cells to cause problems by blocking an effective anti-tumor immune response. The same process, however, plays no role in maintaining immune balance or preventing the misguided immune attack on healthy tissue that leads to autoimmune problems, researchers reported.

 

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When it comes to skin cancer, pictures are worth a thousand words

Senior citizens, the most frequent victims of skin cancer, need to be aware of how to identify dangerous melanoma skin cancers before the spread - see graphics

Aug 2, 2013

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Tide is turning in skin cancer battle with more than 100 promising drugs for blocking cancer-causing signaling pathways

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April 23, 2013

See more links below news report.


 
 

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Blocking this mechanism led to the elimination or dramatic reduction of melanoma by the immune system in mice.

“Regulatory T cells are a major barrier to effective anti-tumor immunity,” said the study’s corresponding author, Dario Vignali, Ph.D., vice chair of the St. Jude Department of Immunology.

“We have identified a mechanism that enhances the ability of regulatory T cells to put the brakes on the immune response in tumors but plays no role in immune system maintenance. For the first time, we may now have an opportunity to selectively target the activity of regulatory T cells for treatment of cancer without inducing autoimmune or inflammatory complications.”

The mechanism is built around two proteins. One, semaphorin-4a (Sema4a), is carried on the surface of various immune cells that can spark inflammation. The other, neuropilin-1 (Nrp1), is carried on the surface of regulatory T cells.

Vignali and his colleagues used a variety of molecular and cellular techniques to show that Sema4a binding to Nrp1 turns on a biochemical pathway in mouse regulatory T cells that enhances their function, stability and survival. When scientists eliminated Nrp1 on just regulatory T cells, those cells were unable to respond to signals that normally bolstered their anti-inflammatory activity.

When investigators analyzed human regulatory T cells, they found evidence that the pathway may also serve the same role.

In addition, more than 16 months after losing Nrp1 activity in their regulatory T cells, the mice showed no signs of autoimmune or inflammatory complications. “That is significant because mice and humans that lack or have substantial defects in regulatory T cells develop lethal autoimmune disease,” Vignali said.

Knocking out or blocking the activity of Nrp1 on regulatory T cells in mouse models of several human cancers, including the deadly skin cancer melanoma, led to reduced, delayed or complete elimination of the tumors. Blocking Sema4a had a similar anti-tumor effect, researchers reported.

“The impact was particularly dramatic in a mouse model of human melanoma,” Vignali said. “Mice lacking Nrp1 on regulatory T cells were almost completely resistant to developing melanoma, but did not develop any autoimmune or inflammatory complications.”

Although investigators have not yet identified which cells carry Sema4a in tumors and boost regulatory T cell function, the scientists did report that immune cells called plasmacytoid dendritic cells (pDCs) provided more than half of the Sema4a in tumors in this study. That was surprising because pDCs make up a very small percentage of immune cells, and there is a long history of suppressive interactions between regulatory T cells and pDCs in tumors, Vignali said. Both cell types are recognized as inducing the immune system to tolerate, rather than attack, tumors.

Researchers also provided new details of how the Nrp1 pathway functions, including evidence that along with bolstering the ability of regulatory T cells to suppress the immune response, the pathway also helps maintain a stable population of regulatory T cells. “This pathway does not just boost regulatory function. It may define how regulatory T cells maintain their identity,” said Greg Delgoffe, Ph.D., a postdoctoral fellow in Vignali’s laboratory. Delgoffe and Seng-Ryong Woo, Ph.D., a former postdoctoral fellow in Vignali’s laboratory, are co-first authors.

The other authors are Meghan Turnis, Cliff Guy, Abigail Overacre, Matthew Bettini, Peter Vogel, David Finkelstein and Creg Workman, all of St. Jude; David Gravano, formerly of St. Jude; and Jody Bonnevier, R&D Systems, Inc., Minneapolis.

The study was funded in part by grants (AI091977, AI039480 and AI098383) from the National Institutes of Health; a grant (CA21765) from the National Cancer Center at NIH; and ALSAC.

Links to More Archived Stories on Melanoma Cancer

About Melanoma

Melanoma is a form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

About 76,250 men and women (44,250 men and 32,000 women) were expected to be diagnosed with and 9,180 men and women to die of melanoma of the skin in 2012.

From 2005-2009, the median age at diagnosis for melanoma of the skin was 61 years of age.

Approximately 0.6% were diagnosed under age 20; 6.8% between 20 and 34; 10.7% between 35 and 44; 18.2% between 45 and 54; 21.6% between 55 and 64; 18.8% between 65 and 74; 16.7% between 75 and 84; and 6.6% 85+ years of age.

The age-adjusted incidence rate was 21.0 per 100,000 men and women per year.

US Mortality

From 2005-2009, the median age at death for melanoma of the skin was 68 years of age. Approximately 0.1% died under age 20; 2.6% between 20 and 34; 5.6% between 35 and 44; 13.5% between 45 and 54; 19.9% between 55 and 64; 21.2% between 65 and 74; 24.1% between 75 and 84; and 12.9% 85+ years of age.

The age-adjusted death rate was 2.7 per 100,000 men and women per year. These rates are based on patients who died in 2005-2009 in the US.

Lifetime Risk

Based on rates from 2007-2009, 1.99% of men and women born today will be diagnosed with melanoma of the skin at some time during their lifetime. This number can also be expressed as 1 in 50 men and women will be diagnosed with melanoma of the skin during their lifetime. These statistics are called the lifetime risk of developing cancer.

Sometimes it is more useful to look at the probability of developing melanoma of the skin between two age groups. For example, 0.99% of men will develop melanoma of the skin between their 50th and 70th birthdays compared to 0.60% for women

Prevalence

On January 1, 2009, in the United States there were approximately 876,344 men and women alive who had a history of melanoma of the skin - 427,810 men and 448,534 women.

>> See the online booklet What You Need To Know About™ Melanoma and Other Skin Cancers

>> Melanoma home page at American Cancer Society

>> Melanoma Home Page at National Cancer Institute

>> Melanoma at Wikipedia

>> American Academy of Dermatology

Immune System Uses Melanoma's Own Proteins to Kill Off Cancer Cells, Researchers Say

Transfer of cancer building cells to immune system provides crucial intelligence about the attacking cancer, which facilitates the right defense to kill the cancer - Feb. 4, 2013

Earlier Detection of Cancer May Be Enhanced by MIT Discovery with Biomarkers Collected in Urine

Nanoparticles amplify tumor signals, making them much easier to detect in urine - Dec. 17, 2012

Small Test Shows Treatment’s Potential to Stop Spread of Melanoma Cancer

Treatment uses drug believed capable of stimulating a patient’s immune system into attacking cancer cells while sparing healthy normal tissue - Nov. 16, 2012

How Melanoma Skin Cancer Can Resist Chemotherapy is Discovered

Study results suggest new approach to treating most deadly skin cancer - Sept. 17, 2012

Discovery of Biomarker for Deadly Melanoma Skin Cancer Offers New Hope

Researchers were able to reverse melanoma growth in pre-clinical studies  - Sept. 13, 2012

Melanoma Skin Cancer May Be More Treatable with New Discovery

Average age of melanoma diagnosis is 61; over 9,000 expected to die in 2012 - more about this skin cancer below news report - Aug. 15, 2012

Secret to Melanoma Cancer’s Resistance to Treatment Exposed - Hope for Seniors

After melanoma removed from head...Researchers say they have found why treatment is difficult and may have answer for turning this around - July 23, 2012


Aspirin, Painkillers Ward Off Skin Cancer; Second Study Lets Immune System Stop Melanoma

NSAIDs decreased risk for squamous cell carcinoma and malignant melanoma; advanced melanoma patients see scientist lower cancer barrier to allow immune system attack - May 29, 2012


Early Success in Curing Melanoma in Mice Spurs Mayo Vaccine Development

Success with melanoma adds to Mayo Clinic's growing portfolio of experimental cancer vaccines - March 19, 2012


New Therapies May Mean More Life for Patients with Advanced Melanoma

Two new drugs, vemurafenib (Zelboraf) and ipilimumab (Yervoy), showing promise in slowing the progression of this skin cancer - March 16, 2012


Metastatic Melanoma Patients Live Almost Twice as Long with New Drug

Zelboraf (vemurafenib) changes the natural history of the disease to extend survival - see video - Feb. 23, 2012


Cancer Survivors Face Increased Risk of Melanoma; Melanoma Survivors Even More

Melanoma the most aggressive, dangerous skin cancer, fifth most common cancer among men, seventh among women - Dec. 19, 2011


Pre-Melanoma Skin Lesion Found Mostly in Elderly Successfully Removed with Laser

Lentigo maligna disappears as carbon dioxide laser exerts its effect by vaporization of water-containing cells - Nov. 21, 2011


Coffee, Favorite Drink of Seniors, Provides Protection from Basal Cell Carcinoma

Women get almost twice as much protection as men among 3-cup a day drinkers - see video - Oct. 26, 2011


Senior Citizens Facing Melanoma Should Worry More About Their Health Than Their Age

Patients with lower muscle density had much higher rates of their cancer returning – regardless of the tumor size or patient's age - Aug. 30, 2011


Vitamin D Appears Linked With Risk of Skin Cancer, Although Relationship Complex

Study looked at vitamin D level in senior citizens with non-melanoma skin cancers - Aug. 15, 2011


Melanoma Skin Cancer a Chronic Disease Causing Long-Term Problems for Women

Women need additional care, including follow-up and possibly counseling to optimally cope with melanoma - Feb. 21, 2011

 

 

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