Nav: Home

Immunotherapy and diabetes: A game of hide and seek?

June 11, 2019

Osaka, Japan - Immune checkpoint inhibitors (ICIs) are an emerging type of cancer immunotherapy that uses the immune system to attack cancer cells. However, in some patients they cause the immune system to attack healthy cells, leading to autoimmune diseases. When pancreatic beta cells are attacked, this can lead to type 1 diabetes. In a case report published in Diabetes Care, researchers from Osaka University provide insight into this unintended consequence of ICIs.

Type 1 diabetes is caused by the destruction of pancreatic beta cells, which produce insulin. Recent clinical studies in patients with cancer have found that ICIs can in rare cases lead to this form of diabetes. Exactly how ICIs might do this, though, is a mystery.

The researchers came across a singular circumstance in a patient with kidney cancer who was treated with ICIs. The situation allowed them to examine tissue stains and take a closer look at the disease. "The patient's cancer had metastasized and spread to his pancreas, which had to be removed," lead author Sho Yoneda explains.

When the team looked at the pancreas, they found the hallmark signs of type 1 diabetes. "We saw substantial infiltration of T cells into the pancreatic tissue and very few surviving beta cells," Yoneda continues. "What was interesting was that the remaining beta cells had little or no expression of the immune tolerance protein PD-L1. This was unexpected, because previous studies had reported elevated PD-L1 in the beta cells of patients with typical autoimmune type 1 diabetes."

PD-L1 tells the immune system that a cell is not a foreign threat. This process, called immune tolerance, stops the immune system from attacking vital tissues and organs--like the pancreas.

"ICIs block the effect of proteins like PD-L1 and essentially shut down immune tolerance," says Iichiro Shimomura, professor at Osaka University and co-author of the study. "This is excellent for treating cancer because tumors often express PD-L1, which allows them to hide from the immune system. The problem is that by shutting down immune tolerance, you increase the likelihood that the immune system will also start to attack healthy tissue."

It remains unclear whether ICIs caused the observed damage to the patient's pancreas, and the role played by PD-L1 is still unclear. "There is still a great deal to be learned about how checkpoint inhibitors contribute to autoimmune diseases," Shimomura adds. "Still, this case suggests that therapies targeting PD-L1 may cause cellular changes that can ultimately lead to type 1 diabetes."
-end-
The article, "T-Lymphocyte Infiltration to Islets in the Pancreas of a Patient Who Developed Type 1 Diabetes After Administration of Immune Checkpoint Inhibitors," was published in Diabetes Care at DOI: 10.2337/dc18-2518.

Osaka University

Related Diabetes Articles:

The role of vitamin A in diabetes
There has been no known link between diabetes and vitamin A -- until now.
Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
Complications of type 2 diabetes affect quality of life, care can lead to diabetes burnout
T2D Lifestyle, a national survey by Health Union of more than 400 individuals experiencing type 2 diabetes (T2D), reveals that patients not only struggle with commonly understood complications, but also numerous lesser known ones that people do not associate with diabetes.
Type 2 diabetes and obesity -- what do we really know?
Social and economic factors have led to a dramatic rise in type 2 diabetes and obesity around the world.
A better way to predict diabetes
An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery.
The Lancet Diabetes & Endocrinology: Older Americans with diabetes living longer without disability, US study shows
Older Americans with diabetes born in the 1940s are living longer and with less disability performing day to day tasks than those born 10 years earlier, according to new research published in The Lancet Diabetes & Endocrinology journal.
Reverse your diabetes -- and you can stay diabetes-free long-term
A new study from Newcastle University, UK, has shown that people who reverse their diabetes and then keep their weight down remain free of diabetes.
New cause of diabetes
Although insulin-producing cells are found in the endocrine tissue of the pancreas, a new mouse study suggests that abnormalities in the exocrine tissue could cause cell non-autonomous effects that promotes diabetes-like symptoms.
The Lancet Diabetes & Endocrinology: Reducing sugar content in sugar-sweetened drinks by 40 percent over 5 years could prevent 1.5 million cases of overweight and obesity in the UK and 300,000 cases of diabetes
A new study published in The Lancet Diabetes & Endocrinology journal suggests that reducing sugar content in sugar sweetened drinks (including fruit juices) in the UK by 40 percent over five years, without replacing them with any artificial sweeteners, could prevent 500,000 cases of overweight and 1 million cases of obesity, in turn preventing around 300,000 cases of type 2 diabetes, over two decades.
Breastfeeding lowers risk of type 2 diabetes following gestational diabetes
Women with gestational diabetes who consistently and continuously breastfeed from the time of giving birth are half as likely to develop type 2 diabetes within two years after delivery, according to a study from Kaiser Permanente published today in Annals of Internal Medicine.

Related Diabetes Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...