Navigation Links
Mayo Clinic: Exhaustion renders immune cells less effective in cancer treatment
Date:5/9/2012

ROCHESTER, Minn. -- Rather than stimulating immune cells to more effectively battle cancerous tumors, treatment with the protein interleukin-12 (IL-12) has the opposite effect, driving these intracellular fighters to exhaustion, a Mayo Clinic study has found. The findings appear in the Journal of Clinical Investigation.The study helps explain the negative results of clinical trials testing the treatment's ability to ramp up the body's natural immune response to destroy cancer cells. The study also demonstrates that the same "T cell exhaustion" that plagues specialized immune cells during chronic viral infections also affects cells fighting long bouts of cancer.

MULTIMEDIA ALERT:: Video of interview excerpts is available on the Mayo Clinic News Network

The results suggest a change in therapeutic tactics for lymphomas and other cancers by dampening, rather than fueling, the effects of cell-signaling molecules such as IL-12.

The study focused on a type of cancer called Follicular B-cell non-Hodgkin's lymphoma (FL), the second most frequent type of non-Hodgkin's lymphoma. Previously, senior author Stephen Ansell, M.D., Ph.D.,a Mayo Clinic hematologist, had shown that tumors biopsied from patients with FL and other similar cancers are a 50-50 mixture of cancer cells and immune cells. Although those immune cells are genetically programmed to kill cancer, instead, they seemed content to cohabitate with their deadly neighbors. Dr. Ansell wondered if a phenomenon known as T cell exhaustion may be the cause. The study findings suggest it is.

"It is like beating a dead horse," says Dr. Ansell. "Our study suggests that many immunotherapy approaches are futile, because these cells are already past the point where they can do their job of targeting and killing malignant cells. Before we can stimulate the immune system, we have to reverse this state of exhaustion so the body's T cells can get back to work."

T cell exhaustion was discovered a few years ago in the context of chronic viral infections such as cytomegalovirus (CMV), hepatitis and HIV. Researchers found that constant unrelenting combat with these viruses caused a key contingent of the immune response, known as T cells, to wear out. Even when artificially stimulated, these exhausted cells were unable to proliferate, recruit other members of the immune army, or kill enemy cells. In addition, these T cells began to carry cellular marks of exhaustion, most notably the cell surface proteins PD1 and Tim-3.

In this study, Dr. Ansell and his colleagues tested whether exposing isolated human T cells to IL-12 would induce T cell exhaustion. They found that treatment with IL-12 brought the Tim-3 marker of exhaustion to the cell surface. When they tried experimentally to stimulate those immune cells into action, they discovered that the T cells couldn't proliferate and couldn't make the immune system signaling molecules known as cytokines.

"We think that IL-12 is useful in the short term, but detrimental in the long term," Dr. Ansell says. "Almost like pouring gasoline on a campfire: You get a really big blaze, but then it all burns down to nothing."

The researchers found that the more cells marked with Tim-3 in a given tumor, the worse the patient's prognosis. They also showed that by blocking Tim-3 they could return the T cells to normal function.

"Once we've worked out all factors that are contributing to exhaustion, the next step will be figuring out which of them can we realistically reverse, particularly in the context of patients," Dr. Ansell says. "Some of these cytokines have a critical role in the body, and we wouldn't want to reverse good effects along with the bad."


'/>"/>
Contact: Joe Dangor
newsbureau@mayo.edu
507-284-5005
Mayo Clinic
Source:Eurekalert

Related medicine news :

1. Mayo Clinic: Obesity epidemic fueling rise in rheumatoid arthritis among women
2. Mayo Clinic: Robotic surgery proves successful, less invasive way to treat HPV-related oral cancer
3. Mayo Clinic: Hospitalization of US underage drinkers common, costs $755 million a year
4. Mayo Clinic: How patients will respond to immunomodulator therapy for multiple myeloma
5. Mayo Clinic: Obese patients with HER2-positive breast cancer may have worse outcomes
6. Mayo Clinic: Young women with rheumatoid arthritis at more risk for broken bones
7. Mayo Clinic: Short training course significantly improves detection of precancerous polyps
8. Mayo Clinic: Primary physicians may hold key to suicide prevention
9. Mayo Clinic: Flaxseed no cure for hot flashes during breast cancer or menopause
10. Mayo Clinic: Raoul Tibes, M.D., Ph.D., to receive Career Development Award
11. Atlanta School of Massage Celebrates 30th Anniversary with a New Green Design and New Name for its Teaching Clinic: SensAbility
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/2/2016)... ... May 02, 2016 , ... Over $60 Billion is spent annually on products ... toys, leading product review site for Toys, Tots, Pets & More (TTPM) announced the ... Spring Showcase at the Metropolitan Pavilion in New York City. , Chosen from a ...
(Date:5/2/2016)... NY (PRWEB) , ... May 02, 2016 , ... This ... reopened for its 2016 guest season which runs through October. Omega is offering a ... . , “There has never been such widespread interest in or need ...
(Date:5/2/2016)... County, CA (PRWEB) , ... May 02, 2016 , ... ... now linking dental health and cognitive decline. According to the research, which was published ... have some degree of cognitive decline, and about 5.4 million Americans have Alzheimer’s disease. ...
(Date:5/2/2016)... (PRWEB) , ... May 02, ... ... researchers report that many commonly used prescription medications, including anxiolytics, painkillers, antidepressants ... mitigate these risks, Novus Medical Detox Center —a leading Florida-based drug ...
(Date:5/2/2016)... Brentwood, TN (PRWEB) , ... May 02, 2016 ... ... American Addiction Centers (AAC) event, will be held at the Bellagio Hotel in ... National Association of Social Work (NASW) will be co-hosting the event. , This ...
Breaking Medicine News(10 mins):
(Date:4/28/2016)... TOKYO , April 28, 2016 /PRNewswire/ ... Ahuja , George Phillips und ... wachsenden Unternehmens    ArisGlobal®, ein ... Life Sciences, gab heute bekannt, dass neue ... wachsenden Unternehmens gestoßen sind, die vielfältige Erfahrungen ...
(Date:4/28/2016)... JERUSALEM , April 28, 2016 ... ), a clinical-stage pharmaceutical company focused on the development of ... participate in the upcoming PIONEERS 2016 conference, presented by ... 5, 2016 in New York . ... overview at the conference. Presentation Details:   ...
(Date:4/27/2016)... April 27, 2016  Hologic, Inc. (Nasdaq: ... results for the fiscal second quarter ended March ... of $0.24 increased 41.2%, and non-GAAP diluted EPS ... increased 5.8% on a reported basis, and 6.3% ... "We posted another good quarter, highlighted by 14.6% ...
Breaking Medicine Technology: