Common autoimmune drug may help reverse immunotherapy-induced diabetes (JAK inhibitors)

Medical Xpress / University of California, Los Angeles / JCI Insight ^ | July 8, 2025 | Dr. Melissa Lechner et al

[ConservativeMind]

A team has identified a potential new strategy to prevent, and even reverse, immune checkpoint inhibitor–induced type 1 diabetes, a rare but life-threatening side effect of cancer immunotherapy, using an existing class of autoimmune drugs.

The study identifies a new group of immune cells involved in the development of immune checkpoint inhibitor–induced type 1 diabetes and shows that JAK inhibitors, which are already FDA-approved for conditions like psoriasis and arthritis, can stop the autoimmune attack on insulin-producing cells in the pancreas and, in some cases, even reverse the damage in preclinical models.

Checkpoint inhibitors like pembrolizumab and nivolumab have revolutionized cancer treatment by activating the immune system to attack tumors, but they can also cause serious autoimmune side effects. More than two-thirds of patients who receive these therapies experience some form of immune-related toxicity.

While rare, one of the most severe is type 1 diabetes, which affects 1–2% of patients and is often permanent. Nearly 90% of those who develop it require ICU care for life-threatening complications and are left insulin-dependent for life.

To better understand the mechanisms, Lechner and her team analyzed immune responses in mice models to see if they could identify the immune cell populations responsible for this toxicity.

The team then tested whether JAK inhibitors, which block the IL-21 and IFNγ pathways, could prevent the onset of immune checkpoint inhibitor–induced type 1 diabetes in mice.

They found the treatment not only blocked the effects of IL-21 and IFNγ, but they were able to reduce the number of Tfh cells and, in some cases, restore normal blood sugar levels, suggesting the potential to not only prevent but also reverse the disease.

"This is the first study to identify Tfh cells and the IL-21/IFNγ pathway as key drivers of checkpoint inhibitor–induced type 1 diabetes," said Lechner.

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TOPICS: Health/Medicine
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[ConservativeMind]

JAK inhibitors are available today to help with this autoimmune issue.

[ConservativeMind]

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