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.
More Diabetes News and Diabetes Current Events

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

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...