Surprise discovery! Immunotherapy may cause diabetes in cancer patients

Photo: Osaka UniversityPancreatic beta cells (insulin-producing) can trigger type 1 diabetes, and recent clinical studies of cancer patients have shown that ICIs can cause diabetes in some rare cases, but the molecular mechanism soutcomes are not clear to researchersResearcher Sho Yoneda explained that the researchers encountered this single condition in patients with kidney cancer treated with ICI, which allowed them to examine the patient's tissues and delve into the causes of the disease, and that the cancer had metastasized and spread to the pancreas, so the patient had to be removedwhen researchers looked at pancreatic tissue, they found signs of type 1 diabetes, and they found that T-cells were flooded with pancreatic tissue in large numbers, and there were few surviving beta cells in the pancreas, much to the interest of researchers, the remaining beta cells were rarely or almost unable to express the immuno-tolerance protein PD-L1, which was completely unexpected to the researchers, since previous studies have shown that high levels of PD-L1 are often expressed in pancreatic beta cells in patients with autoimmune type 1 diabetesPD-L1 tells the body whether the immune system cells are an external threat, a process known as immune tolerance, which blocks the body's immune system from attacking vital organs and tissues of the body, such as pancreatic tissueResearcher Professor Ichiro Shimomura said THAT ICIs can block the effects of proteins such as PD-L1 and turn off immune tolerance, which can effectively treat cancer, because tumors often express PD-L1 proteins, thus avoiding attacks by the immune system, but the current problem is that by turning off immune tolerance, the body increases the likelihood that the immune system will begin to attack healthy tissueit is not clear whether ICIs can cause observable damage to pancreatic tissue in patients, and the role of PD-L1 researchers are not clear, and later researchers need to further study the molecular mechanisms of checkpoint inhibitors that cause autoimmune diseases, the results of the study of this case, which are cited in the paper, suggest that targeted PD-L1 therapy or cell changes and eventually causetype 1 diabetesoriginal origin:Sho Yoneda, Akihisa Imagawa, Yoshiya Hosokawa, et alT.Lymp hocyte Invero to Islets in the Pancreas of A Patient Who Developed Type 1 AfterS Afters Of Ame Checkpoint, Diabet Carees (2019)DOI: 10.2337/dc18-2518