Promising Research Finds Terminally Exhausted T-Cells In Cancer Patients Have The Potential To Be Revived And Improve Immunotherapy
According to the National Cancer Institute, T cells are white blood cells apart of the immune system that “develop from stem cells in the bone marrow and can protect the body from infection and may help fight cancer.”
But, while battling cancer, many patients’ T cells can become so exhausted that they are no longer able to function properly.
And while it is possible for early T cell exhaustion to be reversed via immunotherapy drugs, late-stage T cell exhaustion has long been regarded as irreversible.
Although, promising new research from the University of Pittsburgh Medical Center (UPMC) and the University of Pittsburgh has found otherwise.
The study, which has since been published in Science Immunology, found that even the most exhausted T cells still hold the potential of being revived and becoming functional again.
The research team has also identified new approaches to fight back against T cell exhaustion.
“People think about terminally exhausted T cells as a lost cause, that there’s no coming back from this state,” explained Amanda Pholek, the study’s co-senior author.
“But, given the right circumstances– the T cell version of rest– we show that they can come back.”
The researchers’ findings are based upon an analysis of early and terminally exhausted T cells in mice that had an aggressive melanoma– in which they performed cell epigenome profiling.
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“We expected to find exhausted T cells with epigenomes damaged beyond repair,” Pholek recalled.
But, they discovered the opposite. Pholek and her team found that gene expression could be increased using an antibody known as 4-1BB, which subsequently enhanced T cell activity.
Another crucial finding was that low oxygen levels, also known as hypoxia, significantly contribute to decreased gene expression among exhausted T cells.
“By restoring oxygen or improving co-stimulation, we can realize the full potential of these cells and potentially gain the benefits of a functioning, healthy immune system,” said Greg Delgoffe, the study’s co-senior author.
Now, the researchers are hopeful these findings could inform new approaches to targeting T cell terminal exhaustion– including immunotherapy drugs that specifically target hypoxia, co-stimulation, or engineer exhaustion-resistant T cells known as CAR-T.
To read the study’s complete findings, visit the link here.
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