Navigation Links
Mayo Clinic: Exhaustion renders immune cells less effective in cancer treatment

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
Mayo Clinic

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:
(Date:6/27/2016)... ... June 27, 2016 , ... ... health professionals, announced today its affiliation with Tennessee Counseling Association. This ... the network of the Tennessee Counseling Association, adding exclusive benefits and promotional offers. ...
(Date:6/27/2016)... , ... June 27, 2016 , ... recently awarded ... Eyeglasses . , Millions of individuals in the United States and Canada wear ... a way to both correct vision and make a fashion statement. Even celebrities use ...
(Date:6/26/2016)... ... , ... Pixel Film Studios Released ProSlice Levels, a Media Slicing Effect ... a whole new perspective by using the title layers in ProSlice Levels to ... ProSlice Levels contains over 30 Different presets to choose from. FCPX users ...
(Date:6/26/2016)... Orion, Clarkston, Michigan (PRWEB) , ... June 26, ... ... with respect to fertility once they have been diagnosed with endometriosis. These women ... intercourse but they also require a comprehensive approach that can help for preservation ...
(Date:6/25/2016)... ... ... The temporary closing of Bruton Memorial Library on June 21 due to a possible lice ... overlooked aspect of head lice: the parasite’s ability to live away from a human host, ... a necessary one in the event that lice have simply gotten out of control. , ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... June 23, 2016  MedSource announced today that ... e-clinical software solution of choice.  This latest decision ... value to their clients by offering a state-of-the-art ... relationship establishes nowEDC as the EDC platform of ... full-service clients.  "nowEDC has long been a preferred ...
(Date:6/23/2016)... Calif. , June 23, 2016 Any dentist ... many challenges of the current process. Many of them do ... of the technical difficulties and high laboratory costs involved. And ... to offer it at such a high cost that the ... it. Dr. Parsa Zadeh , founder of ...
(Date:6/23/2016)...  In a startling report released today, National Safety Council ... a comprehensive, proven plan to eliminate prescription opioid overdoses. ... states are tackling the worst drug crisis in recorded U.S. history, ... Kentucky , New Mexico , ... the 28 failing states, three – Michigan , ...
Breaking Medicine Technology: