Improving the Personalization of Immunotherapy Treatments
Considered to be one of the greatest revolutions in cancer treatment, immunotherapy enhances the immune system’s ability to target and destroy cancer cells efficiently. One of the key challenges in immunotherapy is the uncertainty regarding patients’ responses – not all patients respond to the treatment, and some may experience side effects without meaningful therapeutic gain. Therefore, there is a need to identify biomarkers that can predict treatment effectiveness based on individual patient data.
New and promising findings on this topic are now presented in a study led by Prof. Keren Yizhak and Ph.D. student Ofir Shorer from the Rappaport Faculty of Medicine and the Bruce and Ruth Rappaport Cancer Research Center.
Their study is based on a large-scale meta-analysis of single-cell RNA sequencing and T-cell receptor (TCR) sequencing from cancer patients treated with immunotherapy. This allowed them to examine the genetic characteristics of T-cell clones and their influence on treatment success.
T cells are white blood cells that play a crucial role in identifying and destroying cancer cells, as well as protecting the body from external threats like viruses. When T cells recognize a threat, they multiply and form different groups of identical cells known as T cell clones, specialized in fighting that specific threat.
The researchers discovered that while these T cell clones exist in both responsive and non-responsive patients, those who respond to immunotherapy exhibit a unique genetic signature within their T cell clones, and immunotherapy enhances their immune activity. Another key finding was that in non-responsive patients, certain T cell clones were simultaneously found both in the tumor and the bloodstream. The researchers concluded that for improved immune response, it is essential to activate T cell clones found only within the tumor, rather than those present in both the tumor and the blood.
The approach presented by Technion researchers will improve predictive capabilities and may even lead to new treatment strategies that enhance immunotherapy effectiveness. Additionally, these findings provide a deeper understanding of immune system dynamics and their potential to fight cancer, an idea central to immunotherapy.
Prof. Keren Yizhak is a faculty member in the Rappaport Faculty of Medicine. Ofir Shorer is a graduate of the Technion’s Excellence Program and is currently a Ph.D. student on the prestigious M.D./Ph.D. track, which combines clinical studies with advanced research. Also contributing to the research was Asaf Pinhasi, another Ph.D. student in Prof. Yizhak’s research group.
The original study can be found here:
https://www.cell.com/cell-genomics/fulltext/S2666-979X(25)00098-9
