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

Iker Ausejo-Mauleon; Sara Labiano; Daniel de la Nava; Virginia Laspidea; Marta Zalacain; Lucía Marrodán; Marc García-Moure; Marisol González-Huarriz; Irati Hervás-Corpión; Laasya Dhandapani; Silvestre Vicent; Maria Collantes; Iván Peñuelas; Oren J. Becher; Mariella G. Filbin; Li Jiang; Jenna Labelle; Carlos A.O. de Biagi-Junior; Javad Nazarian; Sandra Laternser; Timothy N. Phoenix; Jasper van der Lugt; Mariette Kranendonk; Raoull Hoogendijk; Sabine Mueller; Carlos De Andrea; Ana C. Anderson; Elizabeth Guruceaga; Carl Koschmann; Viveka Nand Yadav; Jaime Gállego Pérez-Larraya; Ana Patiño-García; Fernando Pastor; Marta M. Alonso

doi:10.1016/j.ccell.2023.09.001

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

Iker Ausejo-Mauleon, Sara Labiano, Daniel de la Nava, Virginia Laspidea, Marta Zalacain, Lucía Marrodán, Marc García-Moure, Marisol González-Huarriz, Irati Hervás-Corpión, Laasya Dhandapani, Silvestre Vicent, Maria Collantes, Iván Peñuelas, Oren J. Becher, Mariella G. Filbin, Li Jiang, Jenna Labelle, Carlos A.O. de Biagi-Junior, Javad Nazarian, Sandra LaternserTimothy N. Phoenix, Jasper van der Lugt, Mariette Kranendonk, Raoull Hoogendijk, Sabine Mueller, Carlos De Andrea, Ana C. Anderson, Elizabeth Guruceaga, Carl Koschmann, Viveka Nand Yadav, Jaime Gállego Pérez-Larraya, Ana Patiño-García, Fernando Pastor, Marta M. Alonso

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1911-1926.e8
Journal	Cancer cell
Volume	41
Issue number	11
DOIs	https://doi.org/10.1016/j.ccell.2023.09.001
State	Published - Nov 13 2023
Externally published	Yes

Keywords

diffuse midline glioma
DIPG
DMGs
immune checkpoint
immunotherapy
macrophages
microglia
pediatric brain tumor
TIM-3
tumor microenvironment

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccell.2023.09.001

Cite this

Ausejo-Mauleon, I., Labiano, S., de la Nava, D., Laspidea, V., Zalacain, M., Marrodán, L., García-Moure, M., González-Huarriz, M., Hervás-Corpión, I., Dhandapani, L., Vicent, S., Collantes, M., Peñuelas, I., Becher, O. J., Filbin, M. G., Jiang, L., Labelle, J., de Biagi-Junior, C. A. O., Nazarian, J., ... Alonso, M. M. (2023). TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory. Cancer cell, 41(11), 1911-1926.e8. https://doi.org/10.1016/j.ccell.2023.09.001

Ausejo-Mauleon, I, Labiano, S, de la Nava, D, Laspidea, V, Zalacain, M, Marrodán, L, García-Moure, M, González-Huarriz, M, Hervás-Corpión, I, Dhandapani, L, Vicent, S, Collantes, M, Peñuelas, I, Becher, OJ, Filbin, MG, Jiang, L, Labelle, J, de Biagi-Junior, CAO, Nazarian, J, Laternser, S, Phoenix, TN, van der Lugt, J, Kranendonk, M, Hoogendijk, R, Mueller, S, De Andrea, C, Anderson, AC, Guruceaga, E, Koschmann, C, Yadav, VN, Gállego Pérez-Larraya, J, Patiño-García, A, Pastor, F & Alonso, MM 2023, 'TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory', Cancer cell, vol. 41, no. 11, pp. 1911-1926.e8. https://doi.org/10.1016/j.ccell.2023.09.001

@article{360d50d9ccc74cb2923ecdfa7186116d,

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

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.",

keywords = "diffuse midline glioma, DIPG, DMGs, immune checkpoint, immunotherapy, macrophages, microglia, pediatric brain tumor, TIM-3, tumor microenvironment",

author = "Iker Ausejo-Mauleon and Sara Labiano and {de la Nava}, Daniel and Virginia Laspidea and Marta Zalacain and Luc{\'i}a Marrod{\'a}n and Marc Garc{\'i}a-Moure and Marisol Gonz{\'a}lez-Huarriz and Irati Herv{\'a}s-Corpi{\'o}n and Laasya Dhandapani and Silvestre Vicent and Maria Collantes and Iv{\'a}n Pe{\~n}uelas and Becher, {Oren J.} and Filbin, {Mariella G.} and Li Jiang and Jenna Labelle and {de Biagi-Junior}, {Carlos A.O.} and Javad Nazarian and Sandra Laternser and Phoenix, {Timothy N.} and {van der Lugt}, Jasper and Mariette Kranendonk and Raoull Hoogendijk and Sabine Mueller and {De Andrea}, Carlos and Anderson, {Ana C.} and Elizabeth Guruceaga and Carl Koschmann and Yadav, {Viveka Nand} and {G{\'a}llego P{\'e}rez-Larraya}, Jaime and Ana Pati{\~n}o-Garc{\'i}a and Fernando Pastor and Alonso, {Marta M.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = nov,

day = "13",

doi = "10.1016/j.ccell.2023.09.001",

language = "English (US)",

volume = "41",

pages = "1911--1926.e8",

journal = "Cancer cell",

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number = "11",

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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.

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 - diffuse midline glioma

KW - DIPG

KW - DMGs

KW - immune checkpoint

KW - immunotherapy

KW - macrophages

KW - microglia

KW - pediatric brain tumor

KW - TIM-3

KW - tumor microenvironment

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UR - http://www.scopus.com/inward/citedby.url?scp=85174566994&partnerID=8YFLogxK

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 -

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

Abstract

Keywords

ASJC Scopus subject areas

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