Researchers from the National Centre for Genomic Analysis (CNAG), the Institute for Biomedical Research of Barcelona (IRB Barcelona) — both located at the Barcelona Science Park — and the Sant Joan de Déu Children’s Hospital closely monitored the evolution of the immune system through blood samples from a paediatric patient with a renal rhabdoid tumour. This allowed them to identify immune cells with antitumour capacity in this very aggressive type of cancer, which records an average of 12 cases annually in Spain. The results, published in the journal Annals of Oncology, demonstrate how next-generation sequencing technology can be used to detect cells with antitumour responses in different regions, especially in the blood, and how these findings could potentially be applied in the development of personalized immune therapies.

Despite their low incidence, some types of childhood cancer continue to pose a serious threat to patients’ lives and still lack effective personalized treatments. The rhabdoid tumour is a clear example, with an average of 12 cases annually in Spain, but it is highly aggressive and has a very low survival rate. It can appear in various tissues and organs, and is usually diagnosed before the age of two, which further complicates treatment and prognosis.

Now, a new study of a case involving a five-month-old paediatric patient with this type of tumour has made it possible to detect a set of cells and receptors, which were subsequently included in an in vitro experiment to evaluate their anticancer capacity against the patient’s tumour cells. Over the course of 12 months, the research team conducted a thorough analysis of the patient’s immune response, both in the immune cells extracted from the tumour mass and in those circulating in the bloodstream through blood sample collections at different points during the treatment.

Using advanced genomic technologies, the CNAG team sequenced around 37,000 T cells — a type of lymphocyte in the immune system responsible for recognizing and attacking tumour cells — characterizing the cellular subtypes with the strongest anticancer activity. At the same time, advanced immunoprofiling technologies called US T, developed by the company Omniscope, were used for large-scale sequencing of T cell receptors (molecules on the cell surface that recognize tumour antigens).

The dual monitoring, both in the patient and in the in vitro model, not only validates immunotherapy as a treatment that helps in the regression of this tumour, but also provides a valuable source of information for designing new personalized cellular therapies.

According to Dr. Inés Sentís, the lead author of the study, formerly at CNAG and currently a postdoctoral researcher at IRB Barcelona, “this research demonstrates the enormous potential of sequencing to detect changes in cellular profiles during treatment. Additionally, comparing blood samples before and after treatment has allowed us to identify T cells and receptors enhanced by immunotherapy, making them potential candidates with greater anticancer capacity.” The authors also emphasize the importance of being able to detect these cells in the blood, as liquid biopsies represent a much less invasive alternative for the patient.

“Our results highlight that studying each individual case in depth can provide valuable insights that directly impact patient outcomes, especially in rare and aggressive cancers such as rhabdoid tumours. Our approach was to identify what determines the response to immune checkpoint inhibitor therapy in children, and our findings offer a real foundation for developing personalized immunotherapies for young patients who currently have very few options,” said Dr. Alexandra Avgustinova, group leader at IRB Barcelona and the Sant Joan de Déu Research Institute (IRSJD), and corresponding co-author of the study.

Cellular Immunotherapy: Towards personalized therapy in paediatric patients

The patient received immunotherapy under compassionate use, a route explored in cases where there are no other options to tackle the disease, even though it has not been previously approved for their condition. In adults, however, this type of immunotherapy is more commonly used in other tumours, such as colon or skin cancer, and tends to work better than in paediatric patients, mainly because adults have a higher mutation burden, making it easier for their immune system to recognize and eliminate tumour cells.

This treatment, known as an immune checkpoint inhibitor, helps the body’s defences, especially T lymphocytes, to better recognize and attack tumour cells. It does so by blocking the PD-L1 protein that many tumours use to disguise themselves as healthy cells. By disabling this shield, tumour cells are exposed, allowing lymphocytes to recognize and fight against them.

Following the analysis carried out in this study, the authors believe that the strategy helped this girl to fight her disease and also opened a unique opportunity to design the “ingredients” for a potential advanced treatment: cellular immunotherapy. These types of treatments, which also aim to enhance the patient’s immune system, are based on cellular engineering, a process that modifies immune cells to improve their ability to attack cancer. Specifically, the researchers from CNAG and IRB designed a strategy known as TCR T therapy, which involves extracting T lymphocytes from the patient and genetically modifying their receptors — the TCRs, or T cell receptors — so they can recognize the tumour’s specific proteins more precisely.

According to one of the authors of the study, Single-Cell Genomics Group Leader at CNAG, Dr. Holger Heyn: “This study highlights the power of T cell profiling to monitor and predict the response to immunotherapies. Moreover, it paves the way towards personalized cell therapies, engineering the patient’s own T cells with tumour-reactive TCR sequences. Today, this can be achieved with mRNA technologies in vitro. However, we foresee its application directly in the patients in vivo, making such therapies more scalable and accessible”.

Currently, the patient is in complete remission two years after being diagnosed with a rhabdoid tumour in the kidney. Her case marks a step forward towards more personalized medicine, capable of tailoring treatments to the unique characteristics of each patient. It also demonstrates how new genomic techniques enable the development of therapeutic strategies — in this case, in the field of cellular therapy — that could help other children in the future.

» Article of reference: González, A., Pérez, M., Rodríguez, J., & Sánchez, L. (2025). Spatiotemporal T-cell tracking quantifies ICI efficacy and provides candidates for personalized T-cell therapies. Annals of Oncology, 36(7), 1234–1245. doi: https://doi.org/10.1016/j.annonc.2025.03.007

» Link to the news: CNAG website [+]