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Updated: Jul 14, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory
Iker Ausejo-Mauleon1, Sara Labiano1, Daniel de la Nava1
1Health Research Institute of Navarra (IdiSNA), Pamplona, Spain; Solid Tumor Program, CIMA-Universidad de Navarra, Pamplona, Spain; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.
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.
Insights
Targeting TIM-3 (HAVCR2) in diffuse intrinsic pontine glioma (DIPG) significantly improves survival in preclinical models. This approach harnesses the immune system to fight this aggressive pediatric brain tumor, offering hope for new therapies.
Area of Science:
- Oncology
- Immunology
- Neuro-oncology
Background:
- Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric brain stem tumor with no effective treatments.
- The immune checkpoint TIM-3 (HAVCR2) is implicated in tumor progression and immune evasion.
Purpose of the Study:
- To investigate TIM-3 as a therapeutic target in diffuse intrinsic pontine glioma (DIPG).
- To evaluate the efficacy of TIM-3 inhibition in preclinical DIPG models.
Main Methods:
- Assessment of TIM-3 expression in DIPG tumor cells and the tumor microenvironment (microglia, macrophages).
- Evaluation of TIM-3 inhibition using syngeneic DIPG models.
- Analysis of survival, immune memory, and cytokine/chemokine profiles post-treatment.
Main Results:
- High TIM-3 expression was observed in DIPG tumor cells and associated immune cells.
- TIM-3 inhibition in preclinical models led to prolonged survival and long-term, disease-free survivors.
- TIM-3 blockade promoted an antitumor immune response through direct effects on tumor cells and immune cell activation.
Conclusions:
- TIM-3 is a validated therapeutic target for diffuse intrinsic pontine glioma (DIPG).
- TIM-3 inhibition demonstrates significant potential for clinical translation in treating DIPG.
