Researchers identify new way to unmask melanoma cells to the immune system

January 16, 2018, Duke University Medical Center
Duke scientist are learning more about the process in which melanoma cells hijack dendritic cells, allowing cancer to avoid detection by the immune system. Credit: Alisa Weigandt for Duke Health

system, which enables these deadly skin cancers to grow and spread.

And while new therapies have been effective in releasing the immune 's restraints to unleash the body's own -fighting powers, they only work in about half of patients and often lose their potency as the cancer develops resistance.

Now a research team at the Duke Cancer Institute has found a new way to keep the immune system engaged, and is planning to test the approach in a phase 1 clinical trial. The findings are reported online in the Jan. 16 issue of the journal Immunity.

"Understanding how cancers suppress the immune system is the key to identifying more effective immuno-therapies," said Brent Hanks, M.D., Ph.D., at Duke and senior author of the study. "Our research is an important step in that direction. We've identified a new mechanism of immunotherapy resistance that appears to be reversible, potentially enhancing the effect of the therapies we now have."

Hanks and colleagues, studying genetic mouse models of melanoma and verifying the findings in human specimens, focused on immune system messengers called . These are on high alert for pathogens such as viruses, bacteria and even , signaling the body's T-cell immune fighters into action when sensing harmful invaders.

Somehow, melanomas reprogram dendritic cells so they ignore the cancer, but this process has not been well understood. In the current study, Hanks and colleagues identified a signaling within the tumor microenvironment that melanomas manipulate to silence dendritic cells.

The pathway relies on a regulatory enzyme called IDO, which plays an important role in and is controlled by fatty acid metabolism. Hanks's team found that this is what melanomas compromise, setting in motion a cascade of events that ultimately leads to the immune system tolerating the tumor cells.

Once they identified this pathway, Hanks and colleagues conducted laboratory tests of a molecule that blocks melanoma cells from going stealth, enabling the immune system to mount a direct attack while also enhancing the function of current immunotherapies such as pembrolizumab and nivolumab.

"The IDO enzyme has been a focus of research in recent years, and there are several drugs that are being investigated to target it," Hanks said. "Our research looked at how we might influence the immune suppression function of IDO by targeting it upstream, along the metabolic pathway that controls it.

"We found that this pathway regulates not only IDO but also other important components of the immune system, suggesting that blocking this pathway may be superior to targeting IDO only," Hanks said.

Hanks said a phase 1 clinical study using an existing molecule that targets this newly identified pathway is in the planning stages. It would likely explore whether the investigational drug might boost the success of current immunotherapies.

"While there is understandable excitement around new therapies that enlist the immune system to fight cancer, we are still in a situation where greater than half of patients don't respond in melanoma and the response rate is even worse in other cancer types," Hanks said. "We need to figure out why that is, and figure out how to reverse it. We're hoping this research is a good step in that direction."

Explore further: Rare melanoma type highly responsive to immunotherapy

Related Stories

Rare melanoma type highly responsive to immunotherapy

January 11, 2018
Desmoplastic melanoma is a rare subtype of melanoma that is commonly found on sun-exposed areas, such as the head and neck, and usually seen in older patients. Treatment is difficult because these tumors are often resistant ...

Researchers identify key mutation that suppresses the immune system in melanoma

March 7, 2017
University of California, Irvine researchers have identified a specific mutation that allows melanoma tumor cells to remain undetected by the immune system. The finding may lead to the development of better immunotherapies ...

How a poorly explored immune cell may impact cancer immunity and immunotherapy

November 17, 2017
The immune cells that are trained to fight off the body's invaders can become defective. It's what allows cancer to develop. So most research has targeted these co-called effector T-cells.

Cholesterol byproduct hijacks immune cells, lets breast cancer spread

October 12, 2017
High cholesterol levels have been associated with breast cancer spreading to other sites in the body, but doctors and researchers don't know the cause for the link. A new study by University of Illinois researchers found ...

DNA sensor plays critical role in cancer immunotherapy via response to unexpected DNA form

August 24, 2017
UT Southwestern Medical Center researchers report for the first time that tumors stressed by cancer immunotherapy release their mitochondrial DNA into nearby immune cells, triggering a host alert system.

Study reveals new role for Hippo pathway in suppressing cancer immunity

December 1, 2016
Previous studies identified the Hippo pathway kinases LATS1/2 as a tumor suppressor, but new research led by University of California San Diego School of Medicine scientists reveals a surprising role for these enzymes in ...

Recommended for you

Researchers uncover immune cell dysfunction linked to photosensitivity

August 16, 2018
Researchers at Hospital for Special Surgery (HSS) have discovered that a type of immune cell known as Langerhans appears to play an important role in photosensitivity, an immune system reaction to sunlight that can trigger ...

Chemicals found in vegetables prevent colon cancer in mice

August 14, 2018
Chemicals produced by vegetables such as kale, cabbage and broccoli could help to maintain a healthy gut and prevent colon cancer, a new study from the Francis Crick Institute shows.

Researchers artificially generate immune cells integral to creating cancer vaccines

August 14, 2018
For the first time, Mount Sinai researchers have identified a way to make large numbers of immune cells that can help prevent cancer reoccurrence, according to a study published in August in Cell Reports.

Doctors may be able to enlist a mysterious enzyme to stop internal bleeding

August 14, 2018
Blood platelets are like the sand bags of the body. Got a cut? Platelets pile in to clog the hole and stop the bleeding.

Cannabis link to relieving intestinal inflammation explained

August 13, 2018
Reports from cannabis users that the drug reduces the symptoms of inflammatory bowel disease (IBD) may finally be explained by new research from the University of Massachusetts Medical School and the University of Bath showing ...

Team finds missing immune cells that could fight lethal brain tumors

August 13, 2018
Glioblastoma brain tumors can have an unusual effect on the body's immune system, often causing a dramatic drop in the number of circulating T-cells that help drive the body's defenses.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.