AUG 12, 2022 7:55 AM PDT

Study Suggests that Terminally Exhausted T cells can be Rejuvenated

WRITTEN BY: Carmen Leitch

Our immune cells can target cancer, but T cells can become worn out and exhausted during lengthy battles, and they may stop functioning correctly when that happens. Some immunotherapy drugs can boost the immune system, but it's been thought that after a certain point, T cells could not be rejuvenated any longer. New research has suggested that even terminally exhausted T cells can be revived, however. The findings have been reported in Science Immunology.

Image credit: Pixabay

"People think about terminally exhausted T cells as a lost cause, that there's no coming back from this state," said co-senior study author Amanda Poholek, Ph.D., an assistant professor at the University of Pittsburgh, among other appointments. But of these cells are given the T cell's version of rest, they are able to come back. "This finding could have incredible potential for immunotherapy."

In this study, the researchers used a mouse model of melanoma to characterize T cells as they gradually became more exhausted; epigenetic markers on the genomes of these cells were analyzed. Some parts of the DNA of T cells that were terminally exhausted had opened up, which normally would suggest that genes in that region were active. But in this case, no gene activity was observed in those places. T cells that are fighting tumors may eventually start to lose some functions, which may be due to a loss of proper gene expression.

T cells are fully activated when a receptor is bound, and another stimulatory signal is received. This research suggested that terminally exhausted T cells have lost that extra stimulation. But when an antibody was added, which binds to another receptor called 4-1BB, some gene expression was restored, and T cell activity was enhanced. Even T cells that appeared to be terminally exhausted were able to regain some functions.

"We expected to find exhausted T cells with epigenomes damaged beyond repair, that they were goners," said Poholek. "So, we were really surprised to find that these cells had the potential for recovery."

This study also showed that there were low levels of oxygen in the tumor microenvironment, which disrupts gene expression. The scientists reprogrammed T cells so they would no be impaired by hypoxia, and the cells then became more functional.

It may be possible to stimulate terminally exhausted T cells  through co-stimulation, or by engineering CAR-T cells that resist the effects of hypoxia, added the researchers.

Sources: University of Pittsburgh, Science Immunology

About the Author
BS
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
JUN 21, 2022
Clinical & Molecular DX
Childhood Bronchitis Linked to Pneumonia and Lung Issues in Adulthood
JUN 21, 2022
Childhood Bronchitis Linked to Pneumonia and Lung Issues in Adulthood
Over 50 years ago, researchers began gathering data for the Tasmanian Longitudinal Health Study (TAHS). The TAHS, which ...
AUG 03, 2022
Clinical & Molecular DX
Monkeypox Updates: Transmission, Symptoms, and Treatment
AUG 03, 2022
Monkeypox Updates: Transmission, Symptoms, and Treatment
With the 2020 Covid lockdowns still fresh in our minds, the recent outbreak of monkeypox in the United States has many p ...
AUG 11, 2022
Clinical & Molecular DX
New Tuberculosis Vaccine Enters Phase III Clinical Trial
AUG 11, 2022
New Tuberculosis Vaccine Enters Phase III Clinical Trial
Tuberculosis is a disease caused by the bacterium Mycobacterium tuberculosis. It is spread through the air when a person ...
AUG 09, 2022
Immunology
New Small Molecule May Improve Immunotherapy for a Variety of Cancers
AUG 09, 2022
New Small Molecule May Improve Immunotherapy for a Variety of Cancers
Scientists have been trying to stimulate the immune system to fight cancer for decades, and recent years have brought ma ...
SEP 14, 2022
Drug Discovery & Development
Media Survey Panel vs. Media Screen
SEP 14, 2022
Media Survey Panel vs. Media Screen
Media Survey Panel vs. Media Screen: An Interview with R&D Scientist Catherine Nguyen on Benefit of Using a Media Survey ...
SEP 13, 2022
Immunology
How Cell 'Waste' Boosts Immune Cells' Fight Against Cancer
SEP 13, 2022
How Cell 'Waste' Boosts Immune Cells' Fight Against Cancer
It seems there is a lot more to lactate than we knew.
Loading Comments...