Mapping the Landscape of a Childhood Cancer
Researchers from the Princess Máxima Center for Pediatric Oncology in the Netherlands have made a significant advancement in the fight against neuroblastoma, a malignant nerve tumor affecting children. Their study, recently published in Cancer Cell, utilized advanced single-cell RNA sequencing to analyze 24 tumors from 19 children. This technique allowed an unprecedented view into the individual cancer and immune cells within these tumors.
The Breakthrough in Immune Cell Function
The study's critical finding was the identification of a protein, TIGIT, on the surface of T-cells within the neuroblastoma tumors. TIGIT acts as a brake on T-cells, preventing them from attacking cancer cells effectively. However, the researchers found that this brake could be released using existing checkpoint inhibitor immunotherapies, specifically those targeting TIGIT and another protein, PD-L1.
Promising Lab Results Leading to Clinical Trials
In laboratory settings, including 3D mini-tumors (organoids) and mice models, the combination of checkpoint inhibitors against TIGIT and PD-L1 showed success in killing neuroblastoma cells. This led to an increased survival rate in mice models with recurrent neuroblastoma, simulating the aggressive form of the disease. These promising results have spurred preparations for a clinical study in partnership with the pharmaceutical company Roche, focusing on children with metastatic or recurrent neuroblastoma in Europe and the US.
Experts Weigh In
Dr. Judith Wienke, a senior researcher in the study, highlights the significance of their findings: "In our new study, we have created a high-resolution map of the neuroblastoma immune landscape. This gives us unique insight into how the various immune cells function differently in the tumor. Our immune atlas of neuroblastoma offers important new starting points to improve immunotherapy for this type of childhood cancer.”
Wienke adds, “Our research is still in an early phase, but the results of the new immunotherapy combination in the lab are very encouraging. The next step is to test this experimental treatment in a clinical trial. We will investigate the safety and possible benefit of the combination treatment in children with metastatic or recurrent neuroblastoma.”
Prof. Dr. Jan Molenaar, co-leader of the research, expresses optimism about the rapid translation of this basic research into clinical trials, aiming to enhance the effectiveness of immunotherapy for children with neuroblastoma.
Prof. Dr. Max van Noesel, also involved in the research, notes “In adults, checkpoint inhibitors—therapies that take the brakes off the body’s own immune system—have considerably improved the treatment of, for example, melanoma and lung cancer. But the best-known checkpoint inhibitors, which target the protein PD-L1, have not yet shown any effect in children.”
“Thanks to the single-cell approach in our study, another target, TIGIT, emerged in addition to PD-L1. The preparations for a clinical study into the effect of a combination of TIGIT and PD-L1 blockers are at an advanced stage. I look forward to seeing if this approach, based on basic biological research, will indeed make a difference for children with high-risk or relapsed neuroblastoma.”
The Road Ahead
While the research is still in its early stages, the upcoming clinical trials will be crucial in determining the safety and efficacy of the new immunotherapy combination. The study not only opens a new avenue for treating neuroblastoma but also exemplifies the impact of detailed cellular analysis in understanding and combating cancer.
Original Journal Article:
Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy, Cancer Cell, DOI: 10.1016/j.ccell.2023.12.008.
Researchers from the Princess Máxima Center for Pediatric Oncology in the Netherlands have made a significant advancement in the fight against neuroblastoma, a malignant nerve tumor affecting children. Their study, recently published in Cancer Cell, utilized advanced single-cell RNA sequencing to analyze 24 tumors from 19 children. This technique allowed an unprecedented view into the individual cancer and immune cells within these tumors.
The Breakthrough in Immune Cell Function
The study's critical finding was the identification of a protein, TIGIT, on the surface of T-cells within the neuroblastoma tumors. TIGIT acts as a brake on T-cells, preventing them from attacking cancer cells effectively. However, the researchers found that this brake could be released using existing checkpoint inhibitor immunotherapies, specifically those targeting TIGIT and another protein, PD-L1.
Promising Lab Results Leading to Clinical Trials
In laboratory settings, including 3D mini-tumors (organoids) and mice models, the combination of checkpoint inhibitors against TIGIT and PD-L1 showed success in killing neuroblastoma cells. This led to an increased survival rate in mice models with recurrent neuroblastoma, simulating the aggressive form of the disease. These promising results have spurred preparations for a clinical study in partnership with the pharmaceutical company Roche, focusing on children with metastatic or recurrent neuroblastoma in Europe and the US.
Experts Weigh In
Dr. Judith Wienke, a senior researcher in the study, highlights the significance of their findings: "In our new study, we have created a high-resolution map of the neuroblastoma immune landscape. This gives us unique insight into how the various immune cells function differently in the tumor. Our immune atlas of neuroblastoma offers important new starting points to improve immunotherapy for this type of childhood cancer.”
Wienke adds, “Our research is still in an early phase, but the results of the new immunotherapy combination in the lab are very encouraging. The next step is to test this experimental treatment in a clinical trial. We will investigate the safety and possible benefit of the combination treatment in children with metastatic or recurrent neuroblastoma.”
Prof. Dr. Jan Molenaar, co-leader of the research, expresses optimism about the rapid translation of this basic research into clinical trials, aiming to enhance the effectiveness of immunotherapy for children with neuroblastoma.
Prof. Dr. Max van Noesel, also involved in the research, notes “In adults, checkpoint inhibitors—therapies that take the brakes off the body’s own immune system—have considerably improved the treatment of, for example, melanoma and lung cancer. But the best-known checkpoint inhibitors, which target the protein PD-L1, have not yet shown any effect in children.”
“Thanks to the single-cell approach in our study, another target, TIGIT, emerged in addition to PD-L1. The preparations for a clinical study into the effect of a combination of TIGIT and PD-L1 blockers are at an advanced stage. I look forward to seeing if this approach, based on basic biological research, will indeed make a difference for children with high-risk or relapsed neuroblastoma.”
The Road Ahead
While the research is still in its early stages, the upcoming clinical trials will be crucial in determining the safety and efficacy of the new immunotherapy combination. The study not only opens a new avenue for treating neuroblastoma but also exemplifies the impact of detailed cellular analysis in understanding and combating cancer.
Original Journal Article:
Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy, Cancer Cell, DOI: 10.1016/j.ccell.2023.12.008.