Blocking Immune Molecule Prolongs Survival in Models of the Most Aggressive Childhood Cancer

Researchers from Cima and the Clínica Universidad de Navarra, together with the international cooperative group Diffuse Midline Glioma (DMG-ACT), have confirmed that blocking an immune control molecule reduces the tumor and prolongs survival in animal models of childhood cancer. aggressive .

This research, framed in the Cancer Center Clínica Universidad de Navarra, demonstrates that the inhibition of TIM-3 favors the immune memory of diffuse intrinsic trunk glioma (DIPG) and improves the prognosis of the disease .

DIPG is an aggressive brainstem tumor and the leading cause of pediatric cancer-related death. Due to its location, therapeutic options are limited, so it is essential to study effective treatments. “In recent years, immunotherapy has proven to be an alternative for many types of cancer. Specifically, immune checkpoint inhibitors (key regulators of the immune system) have demonstrated good results in various solid tumors. But due to the unique tumor microenvironment of DIPGs, classic inhibitors have not been effective in these pediatric patients ,” explains Iker Ausejo-Mauleon, predoctoral researcher at the Advanced Therapies Group for Pediatric Solid Tumors at Cima.and first author of the work.

Antitumor immune response

In recent years, the presence of the TIM-3 checkpoint in tumor cells has been related to the proliferation and metastasis capacity of different types of cancer. “In this study, we demonstrated that T IM-3 is also highly expressed both in tumor cells and in cells of the DIPG microenvironment ,” explains Dr. Marta Alonso , co-director of the Cima Solid Tumors Program and director of the study. The results have been published in the latest issue of the scientific journal Cancer Cell.

The next step was to block this molecule and they verified that its inhibition promotes a pro-inflammatory tumor microenvironment that favors a powerful antitumor immune response. “As a consequence, the long-term survival of experimental models increases. Therefore, TIM-3 is presented as a therapeutic target that can guide the development of clinical trials for these patients ,” the researchers point out.

Reference: Ausejo-Mauleon I, Labiano S, De La Nava D, et al. TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory. Cancer Cell. 2023:S1535610823003185. doi: 10.1016/j.ccell.2023.09.001

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