Scientific publications

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

Oct 3, 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


Abstract

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.