Kranendonk, M. (Mariette)

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    TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory
    (Elsevier, 2023) Ausejo-Mauleón, I. (Iker); Labiano, S. (Sara); Nava-Martín, D. (Daniel) de la; Laspidea, V. (Virginia); Zalacain, M. (Marta); Marrodán, L. (Lucía); Garcia-Moure, M. (Marc); Gonzalez-Huarriz, M. (Marisol); Hervás-Corpión, I. (Irati); Dhandapani, L. (Laasya); Vicent, S. (Silvestre); Collantes, M. (María); Peñuelas-Sanchez, I. (Ivan); Becher, O.J. (Oren J.); Filbin, M.G. (Mariella G.); Jiang, L. (Li); Labelle, J. (Jenna); Biagi-Junior, C.A.O. (Carlos A. O.) de; Nazarian, J. (Javad); Laternser, S. (Sandra); Phoenix, T.N. (Timothy N.); Lugt, J. (Jasper) van der; Kranendonk, M. (Mariette); Hoogendijk, R. (Raoull); Mueller, S. (Sabine); Andrea, C.E. (Carlos Eduardo) de; Guruceaga, E. (Elizabeth); Gallego-Perez-Larraya, J. (Jaime); Patiño-García, A. (Ana); Pastor, F. (Fernando); Alonso, M.M. (Marta M.)
    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.