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Research reveals stem-like T cells as crucial to maintaining long-term immune responses
In a groundbreaking study, researchers have discovered a rare type of immune cell, known as stem-like T cells, that could hold the key to overcoming one of the biggest challenges in treating cancer and chronic diseases. A team of scientists from the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and the Peter MacCallum Cancer Centre (Peter Mac) led the study, which sheds light on how these cells could provide lasting immune protection, even in the face of prolonged illnesses.
Published in Science Immunology, the study reveals that these stem-like T cells are sustained by a protein called ID3, expressed by the gene of the same name. These ID3+ T cells have a remarkable ability to self-renew and resist exhaustion, unlike other T cells that typically lose their function over time. This self-sustaining nature allows them to maintain long-term immune responses against chronic infections and cancer, providing hope for more effective and enduring treatments.
Catarina Gago da Graça, Ph.D. Candidate at the Doherty Institute and co-first author of the study, emphasized the significance of these findings. “ID3+ T cells have the remarkable ability to resist burnout and maintain a powerful immune response over time, making them particularly effective in the face of chronic infections or cancer,” said Gago da Graça.
The research also uncovered that certain signals in the body could increase the production of ID3+ T cells, potentially enhancing the efficacy of existing therapies such as CAR T cell treatment. While CAR T therapy has revolutionized cancer treatment, its effectiveness can diminish due to T cell exhaustion. According to Professor Ricky Johnstone, Executive Director of Cancer Research at Peter Mac and co-lead author, boosting ID3+ T cell activity could strengthen the endurance of these cells, leading to more durable therapies.
“We discovered that ID3+ T cell formation could be promoted by specific inflammatory cues, offering new strategies to boost the number of immune cells that excel at fighting cancer in patients,” said Professor Johnstone. “This could lead to better treatments for cancer patients and improved outcomes in clinical immunotherapy.”
The study also holds promise for advancing immunotherapy treatments and the development of vaccines that provide long-lasting protection. Dr. Daniel Utzschneider, Laboratory Head at the Doherty Institute and co-author of the study, highlighted the potential impact of these findings in treating chronic diseases such as HIV, hepatitis B, and hepatitis C.
“Exhausted immune cells remain one of the biggest challenges in treating chronic diseases,” said Dr. Utzschneider. “This research provides a roadmap for how we might reinvigorate the immune system, improving health outcomes for people living with cancer or chronic infections.”
This research is the result of a collaborative effort between the Doherty Institute, Peter Mac, La Trobe University, Northwestern University (U.S.), the Olivia Newton-John Cancer Research Institute, the University of Birmingham (UK), and the University of Melbourne.
Disclaimer: The findings from this study are still in the early stages, and while they offer promising avenues for treatment, more research is needed before they can be applied in clinical settings. Always consult healthcare professionals for medical advice and treatment options.
More information: Catarina Gago da Graça et al, Stem-like memory and precursors of exhausted T cells share a common progenitor defined by ID3 expression, Science Immunology (2025). DOI: 10.1126/sciimmunol.adn1945
Journal information: Science Immunology
