A collaborative team in Spain has used single-cell sequencing and T cell receptor (TCR) profiling to trace the immune response of an infant with a malignant rhabdoid tumor of the kidney, offering one of the most detailed views yet into how immunotherapy can help children with rare and aggressive cancers.
Diagnosed at five months old, the patient underwent surgery, chemotherapy, and radiotherapy at Sant Joan de Déu Hospital in Barcelona, followed by compassionate-use immune checkpoint inhibitor (ICI) therapy. Researchers from CNAG and IRB Barcelona then analyzed immune cells from the tumor and blood over the course of a year. Their study focused on identifying the T cells responsible for keeping the cancer in check.
Using single-cell RNA sequencing of 37,000 T cells and high-throughput TCR sequencing (OS-T, Omniscope), the team tracked the expansion and sustained activity of tumor-reactive T cells. “Our study highlights the enormous potential of sequencing technologies to track changes in immune cell profiles during treatment,” said Inés Sentís of IRB Barcelona.
The researchers later confirmed these cells’ tumor-killing capabilities in vitro. “This study highlights the power of T cell profiling to monitor and predict the response to immunotherapies,” said Holger Heyn, who leads the Single-Cell Genomics Group at CNAG.
Building on these findings, the team designed a TCR-T cell therapy approach using the patient’s own modified T cells. The patient remains in complete remission two years after diagnosis. While the approach is still early-stage, the results point toward a framework for developing more individualized therapies for pediatric cancers with limited treatment options.
Publication Details
Sentís, I., Melero, J. L., Cebria-Xart, A., Grzelak, M., Soto, M., Michel, A., Rovira, Q., Rodriguez-Hernandez, C. J., Caratù, G., Urpi, A., Sauvage, C., Mendizabal-Sasieta, A., Maspero, D., Lavarino, C. E., Pascual-Reguant, A., Heredia, C., Perez, M., Mora, J., Harari, A., & Nieto, J. C. (n.d.). Spatiotemporal T cell tracking for personalized T cell receptor T cell therapy designs in childhood cancer. Annals of Oncology. https://doi.org/10.1016/j.annonc.2025.05.530
Diagnosed at five months old, the patient underwent surgery, chemotherapy, and radiotherapy at Sant Joan de Déu Hospital in Barcelona, followed by compassionate-use immune checkpoint inhibitor (ICI) therapy. Researchers from CNAG and IRB Barcelona then analyzed immune cells from the tumor and blood over the course of a year. Their study focused on identifying the T cells responsible for keeping the cancer in check.
Using single-cell RNA sequencing of 37,000 T cells and high-throughput TCR sequencing (OS-T, Omniscope), the team tracked the expansion and sustained activity of tumor-reactive T cells. “Our study highlights the enormous potential of sequencing technologies to track changes in immune cell profiles during treatment,” said Inés Sentís of IRB Barcelona.
The researchers later confirmed these cells’ tumor-killing capabilities in vitro. “This study highlights the power of T cell profiling to monitor and predict the response to immunotherapies,” said Holger Heyn, who leads the Single-Cell Genomics Group at CNAG.
Building on these findings, the team designed a TCR-T cell therapy approach using the patient’s own modified T cells. The patient remains in complete remission two years after diagnosis. While the approach is still early-stage, the results point toward a framework for developing more individualized therapies for pediatric cancers with limited treatment options.
Publication Details
Sentís, I., Melero, J. L., Cebria-Xart, A., Grzelak, M., Soto, M., Michel, A., Rovira, Q., Rodriguez-Hernandez, C. J., Caratù, G., Urpi, A., Sauvage, C., Mendizabal-Sasieta, A., Maspero, D., Lavarino, C. E., Pascual-Reguant, A., Heredia, C., Perez, M., Mora, J., Harari, A., & Nieto, J. C. (n.d.). Spatiotemporal T cell tracking for personalized T cell receptor T cell therapy designs in childhood cancer. Annals of Oncology. https://doi.org/10.1016/j.annonc.2025.05.530