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

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.

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