TY - JOUR
T1 - TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory
AU - Ausejo-Mauleon, Iker
AU - Labiano, Sara
AU - de la Nava, Daniel
AU - Laspidea, Virginia
AU - Zalacain, Marta
AU - Marrodán, Lucía
AU - García-Moure, Marc
AU - González-Huarriz, Marisol
AU - Hervás-Corpión, Irati
AU - Dhandapani, Laasya
AU - Vicent, Silvestre
AU - Collantes, Maria
AU - Peñuelas, Iván
AU - Becher, Oren J.
AU - Filbin, Mariella G.
AU - Jiang, Li
AU - Labelle, Jenna
AU - de Biagi-Junior, Carlos A.O.
AU - Nazarian, Javad
AU - Laternser, Sandra
AU - Phoenix, Timothy N.
AU - van der Lugt, Jasper
AU - Kranendonk, Mariette
AU - Hoogendijk, Raoull
AU - Mueller, Sabine
AU - De Andrea, Carlos
AU - Anderson, Ana C.
AU - Guruceaga, Elizabeth
AU - Koschmann, Carl
AU - Yadav, Viveka Nand
AU - Gállego Pérez-Larraya, Jaime
AU - Patiño-García, Ana
AU - Pastor, Fernando
AU - Alonso, Marta M.
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2023/11/13
Y1 - 2023/11/13
N2 - 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.
AB - 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.
KW - DIPG
KW - DMGs
KW - TIM-3
KW - diffuse midline glioma
KW - immune checkpoint
KW - immunotherapy
KW - macrophages
KW - microglia
KW - pediatric brain tumor
KW - tumor microenvironment
UR - https://www.scopus.com/pages/publications/85174566994
U2 - 10.1016/j.ccell.2023.09.001
DO - 10.1016/j.ccell.2023.09.001
M3 - Article
C2 - 37802053
AN - SCOPUS:85174566994
SN - 1535-6108
VL - 41
SP - 1911-1926.e8
JO - Cancer Cell
JF - Cancer Cell
IS - 11
ER -