Document Type
Article
Publication Date
11-13-2023
Identifier
DOI: 10.1016/j.ccell.2023.09.001
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.
Journal Title
Cancer cell
Volume
41
Issue
11
First Page
1911
Last Page
1926
Keywords
DIPG; DMGs; TIM-3; diffuse midline glioma; immune checkpoint; immunotherapy; macrophages; microglia; pediatric brain tumor; tumor microenvironment
Recommended Citation
Ausejo-Mauleon I, Labiano S, de la Nava D, et al. Tim-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory. Cancer Cell. 2023;41(11):1911-1926. doi:10.1016/j.ccell.2023.09.001
Comments
This article is available under the Creative Commons CC-BY-NC license and permits non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited.
Publisher's Link: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00318-5