Chronic diseases such as cancer and ongoing infections can lead to an overwhelmed immune system, where T cells, the body’s primary defenders, become less effective. A team of researchers from the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and the Peter MacCallum Cancer Centre (Peter Mac) has uncovered a unique group of immune cells known as stem-like T cells, which are crucial for sustaining strong, long-lasting immune responses.
In a study published in Science Immunology, scientists discovered that the longevity of these stem-like T cells is supported by a protein named ID3, produced by a corresponding gene. These ID3+ T cells possess a distinctive capability to regenerate themselves and resist fatigue, allowing them to maintain immune responses significantly longer than T cells that lack ID3 expression.
Catarina Gago da Graça, a PhD candidate at the Doherty Institute from the University of Melbourne, remarked that this research underlines the significance of ID3+ T cells in addressing one of the primary obstacles faced in treating chronic illnesses: immune exhaustion.
“ID3+ T cells are exceptional in their ability to avoid exhaustion and uphold a robust immune response over extended periods, making them especially effective against persistent infections or cancer,” commented Gago da Graça, who co-authored the study.
The research also indicated that particular signals within the body could enhance the production of ID3+ T cells, which may improve treatments such as CAR T cell therapy. Although CAR T therapy has proven revolutionary for certain cancers, its effectiveness tends to diminish over time due to T cell fatigue.
Professor Ricky Johnstone, Executive Director of Cancer Research at Peter Mac and a co-lead author of the study, explained that boosting ID3 function could improve the stamina of these T cells, leading to more effective and durable therapies.
“We found that the formation of ID3+ T cells could be stimulated by specific inflammatory signals, possibly opening new avenues for increasing the number of immune cells that excel in combating cancer in patients,” noted Professor Johnstone.
“This could result in enhanced treatment options for cancer patients and better overall outcomes in clinical immunotherapy.”
Dr. Daniel Utzschneider, Laboratory Head at the Doherty Institute from the University of Melbourne, stated that these findings could pave the way for advancements in immunotherapy and the creation of vaccines that offer prolonged protection.
“Exhausted immune cells present one of the most significant challenges in managing chronic diseases,” Dr. Utzschneider said.
“This research provides a blueprint for how we can potentially revitalize the immune system and enhance health outcomes for individuals affected by cancer or chronic infections like HIV and hepatitis B or C, thanks to these stem-like T cells, which are the hidden strength of the immune system.”
This study resulted from a collaborative initiative between the Doherty Institute, Peter Mac, La Trobe University, Northwestern University (USA), the Olivia Newton-John Cancer Research Institute, the University of Birmingham (UK), and the University of Melbourne.
