A study led by UCLA has discovered that JAK inhibitors could potentially prevent or reverse immune-related diabetes triggered by cancer immunotherapy. Immune checkpoint inhibitors have revolutionized cancer treatment by utilizing the body’s own immune system to combat tumors. However, some individuals face a significant drawback as a result. A rare and hazardous side effect known as ICI-induced type 1 diabetes can emerge unexpectedly, leading to the destruction of insulin-producing cells in the pancreas. This forces patients into a lifelong dependency on insulin and exposes them to severe complications like ketoacidosis.
While prior research identified CD8+ T cells as contributors to this harm, a new investigation has uncovered a previously underestimated culprit. Scientists, headed by Dr. Melissa Lechner at UCLA, revealed the potential role of CD4+ T follicular helper (Tfh) cells in causing this condition. These cells release signaling molecules such as IL-21 and interferon gamma (IFN-γ), which prompt the immune system to attack the body’s tissues. The study, published in JCI Insight, presents a promising approach for patients. Existing JAK inhibitors, approved for treating autoimmune disorders like arthritis and psoriasis, could potentially prevent or even reverse this form of diabetes.
JAK inhibitors, already sanctioned by the FDA for conditions such as psoriasis and arthritis, have demonstrated the ability to halt the autoimmune assault on insulin-producing cells in the pancreas and, in certain instances, reverse the damage. Immune-related adverse events, like ICI-induced type 1 diabetes, occur in approximately two-thirds of patients undergoing checkpoint inhibitor treatments like pembrolizumab and nivolumab. Despite their success in combating cancer cells, these drugs can also incite immune attacks on healthy organs.
The development of ICI-T1DM can be swift and silent, with patients often requiring urgent care upon its onset. This condition affects about 1–2% of individuals undergoing checkpoint therapies, and the majority of those affected need emergency intervention at the initial manifestation. Once established, there is no known cure, necessitating lifelong insulin usage even if the cancer is eradicated. The swift and lasting nature of ICI-T1DM poses significant challenges for patients undergoing treatment for curable cancers, potentially impacting them for years to come.
Explore more: [Link to UCLA Health Sciences article]
The immune system can cause serious harm by attacking the body’s own pancreatic beta cells responsible for producing insulin. A potential solution was identified by a research team who discovered that JAK inhibitors could block the action of harmful immune signals, potentially halting the autoimmune response. These drugs, already used for conditions like alopecia and rheumatoid arthritis, show promise in protecting against autoimmune damage caused by immune checkpoint therapy in cancer patients.
When JAK inhibitors were given to mice receiving immune checkpoint therapy, there was a significant reduction in harmful Tfh cells in the pancreas, protecting beta cells from destruction and even restoring normal blood sugar levels in some cases. Human samples also supported these findings, showing lower levels of Tfh cells and reduced autoimmune markers in patients who received JAK inhibitors. This breakthrough demonstrates the potential to block the IL-21 and IFN-γ pathway using existing drugs without compromising the immune system’s ability to fight cancer.
The research team believes that intervening in these toxicities could significantly benefit patients undergoing immunotherapy, especially for early-stage cancers. The discovery may also have broader implications beyond diabetes, potentially preventing other autoimmune side effects affecting vital organs like the thyroid, heart, liver, or lungs. JAK inhibitors have shown promise in other checkpoint-related conditions, with trials demonstrating improved survival rates in patients with certain autoimmune complications.
The next step for the researchers is to launch a human trial testing the efficacy of JAK inhibitors in cancer patients experiencing immune checkpoint-related diabetes. If successful, this approach could become a vital tool in preventing or reversing severe side effects of cancer immunotherapy, making treatment safer for patients with pre-existing autoimmune conditions.
Lechner emphasized that by including ten individuals who were previously excluded from trials, the reach of these therapies can be expanded. This can provide real solutions for the numerous patients experiencing permanent side effects. As checkpoint inhibitors become increasingly prevalent in cancer treatment, it is crucial to find ways to mitigate their risks without compromising their benefits. The identification of Tfh cells’ involvement in ICI-T1DM and the potential of JAK inhibitors to halt them represent a significant advancement in enhancing the safety of these life-saving treatments for all individuals. This article was sourced from The Brighter Side of News. If you enjoy uplifting stories like this, consider subscribing to The Brighter Side of News’ newsletter.
