Scientists have discovered a mechanism to reinvigorate the immune system, which could prevent it from declining as it battles chronic infections and long-term illnesses such as cancer. This discovery could enhance treatment efficacy and improve clinical prognosis.
Fighting chronic disease is like running a marathon, and T cells, the immune system's frontline defenders, are the runners. As soon as the starting gun goes off, the players sprint quickly and powerfully. However, the longer a marathon goes, the more runners' energy reserves are depleted, making reaching the finish line -- say, eradicating cancer -- increasingly difficult.
New research led by the Peter Doherty Institute for Infection and Immunity and the Peter MacCallum Cancer Center (Peter Mac) in Melbourne has discovered a rare type of T cell with the ability to self-renew that may be the answer to achieving long-lasting immune responses against chronic disease.
Dr Daniel Utzschneider, Laboratory Director of the Department of Microbiology and Immunology at the University of Melbourne's Doherty Institute and one of the study's corresponding authors, said: "Exhausted immune cells remain one of the biggest challenges in treating chronic diseases. This study provides a roadmap for how we can reinvigorate the immune system and improve health in patients with cancer or chronic infections such as HIV or hepatitis B and C, thanks to these stem-like T cells - the secret power of the immune system."
Stem-like T cells, as the name suggests, are a subset of T cells with stem cell characteristics. Their "dryness" gives them the ability to self-renew and resist failure. The researchers discovered that stem T cell endurance is fueled by a protein called inhibitor of DNA binding 3 (or ID3), which is expressed by a gene of the same name.
"ID3+ T cells have an extraordinary ability to resist burnout and maintain strong immune responses over long periods of time, making them particularly effective in the face of chronic infections or cancer," said Catarina Gagoda Graça, co-first author of the study and a doctoral student at the Doherty Institute.
The researchers found that certain signaling pathways in the body increase the number of ID3+ T cells, paving the way for the development of more effective immunotherapies, such as CAR-T cell therapy, which decreases in effectiveness over time as the cells become "exhausted" of their capacity.
"We found that the formation of ID3+ T cells can be promoted by specific inflammatory cues, which may provide new strategies to increase the number of immune cells in patients that are good at fighting cancer," said Professor Ricky Johnstone, the study's other co-first author and executive director of Peter Mack Cancer Research. "This may lead to better treatments for cancer patients and improve the effectiveness of clinical immunotherapy."
In addition to more effective immunotherapies, insights gained from this study could lead to vaccines that offer longer-lasting protection, the researchers say. Also involved in the study were La Trobe University in Australia, the University of Melbourne, the Olivia Newton-John Cancer Institute, the University of Birmingham in the UK and Northwestern University in the US.
The research was published in the journal ScienceImmunology.