New research in The Journal of Immunology uncovers how high blood sugar (hyperglycemia) and type 1 diabetes (T1D) may protect against certain cancers like melanoma, breast and colon cancer. T1D has been associated with a decreased risk of certain cancers, but the exact reasons why have remained a mystery. New data from studies in mice, now shows that it could be due to changes in immune cells, called T cells, caused by hyperglycemia.
How Does Hyperglycemia Change T Cells?
To untangle why patients with T1D have a decreased risk of certain cancers, the researchers first observed that tumor growth in mice with hyperglycemia, like in untreated T1D, was reduced when compared to diabetic mice receiving insulin and mice with normal blood sugar levels.
When the researchers investigated what caused the tumors to grow slower in hyperglycemic mice, they found that hyperglycemia was reprogramming T cells to better control of tumor growth.
The hyperglycemic mice not only had a greater number of T cells, but those T cells were found to be more effective at fighting tumors. The researchers say this is likely because hyperglycemia causes the body to maintain more inflammatory immune cells, which contributes to their cancer-fighting ability. Interestingly, when T1D mice received insulin to control their blood sugar, the T cells lost their heightened cancer fighting abilities.
An Alternate Way to Send Signals
To better understand the specific changes in the T cells from hyperglycemic mice, the researchers compared T cells from hyperglycemic mice, diabetic mice receiving insulin, and mice with normal blood sugar levels to identify the changes that caused the heightened cancer fighting ability.
The researchers found that T cells from hyperglycemic mice had an increase in their use of a particular cellular signaling pathway, which contributed to the T cells increased cancer fighting ability. Identifying this signaling pathway as an important factor that enhances the tumor-fighting abilities of T cells, is key to developing new cancer treatments that could mimic this enhancement.
After observing the differences in mice, the researchers also looked for similar changes in people and found that the same signaling pathway was also increased in immune cells from blood taken from people with hyperglycemia.
Developing Cancer Treatments
“Our findings open several research avenues for new cancer immunotherapies by applying the changes we see in T cells of patients with type 1 diabetes and mimicking those cell changes in new treatments for all patients, said Dr. Anamika Bose, Assistant Professor at the National Institute of Pharmaceutical Education and Research in India, and senior author of the study.
“These findings are exciting, because we now partly understand how T1D protects against certain cancers. Our new understanding of the involvement of this specific signaling pathway provides us with new ways to develop T cell-based immunotherapies for cancer patients,” said Dr. Bose.
