Scientific publications

TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory

Nov 13, 2023 | Magazine: Cancer Cell

Iker Ausejo-Mauleon  1 , Sara Labiano  1 , Daniel de la Nava  1 , Virginia Laspidea  1 , Marta Zalacain  1 , Lucía Marrodán  1 , Marc García-Moure  1 , Marisol González-Huarriz  1 , Irati Hervás-Corpión  1 , Laasya Dhandapani  1 , Silvestre Vicent  2 , Maria Collantes  3 , Iván Peñuelas  4 , Oren J Becher  5 , Mariella G Filbin  6 , Li Jiang  6 , Jenna Labelle  6 , Carlos A O de Biagi-Junior  6 , Javad Nazarian  7 , Sandra Laternser  8 , Timothy N Phoenix  9 , Jasper van der Lugt  10 , Mariette Kranendonk  10 , Raoull Hoodendijk  10 , Sabine Mueller  11 , Carlos De Andrea  12 , Ana C Anderson  13 , Elizabeth Guruceaga  14 , Carl Koschmann  15 , Viveka Nand Yadak  16 , Jaime Gállego Pérez-Larraya  17 , Ana Patiño-García  1 , Fernando Pastor  18 , Marta M Alonso  19


Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain stem tumor and the leading cause of pediatric cancer-related death. To date, these tumors remain incurable, underscoring the need for efficacious therapies.

In this study, we demonstrate that the immune checkpoint TIM-3 (HAVCR2) is highly expressed in both tumor cells and microenvironmental cells, mainly microglia and macrophages, in DIPG. We show that inhibition of TIM-3 in syngeneic models of DIPG prolongs survival and produces long-term survivors free of disease that harbor immune memory.

This antitumor effect is driven by the direct effect of TIM-3 inhibition in tumor cells, the coordinated action of several immune cell populations, and the secretion of chemokines/cytokines that create a proinflammatory tumor microenvironment favoring a potent antitumor immune response.

This work uncovers TIM-3 as a bona fide target in DIPG and supports its clinical translation.

CITATION  Cancer Cell. 2023 Oct 3:S1535-6108(23)00318-5.  doi: 10.1016/j.ccell.2023.09.001.

Our authors

Investigador predoctoral del Programa de Terapias Moleculares del Cima Universidad de Navarra
Dr. Iker Ausejo Mauleón
Dr. Sara Labiano Almiñana
Daniel de la Nava Martín
Dr. Virginia Laspidea Ustés
Lucía Marrodán Fernández
Laboratory technician Solid Tumor Research Program
Dr. Marc García Moure
Dr. Marisol González Huarriz
Research Technician Solid Tumor Research Program
Dr. Irati Hervás Corpión
Dr. Lassya Dhandapani