Related Experiment Video
Updated: Aug 29, 2025
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Immunoglobulin-like transcript 2 blockade restores antitumor immune responses in glioblastoma
Seila Lorenzo-Herrero1,2,3, Christian Sordo-Bahamonde1,2,3, Alejandra Martínez-Pérez1,2,3
1Department of Functional Biology, Immunology, Universidad de Oviedo, Oviedo, Spain.
Abstract:
Glioblastoma stands as the most frequent primary brain tumor. Despite the multimodal therapy for glioblastoma patients, the survival rate is very low, highlighting the need for novel therapies that improve patient outcomes. Immune checkpoint blockade strategies are achieving promising results in a myriad of tumors and several studies have reported its efficacy in glioblastoma at a preclinical level. ILT2 is a novel immune checkpoint that exerts an inhibitory effect via the interaction with classical and non-classical HLA class-I molecules. Herein, we report that ILT2 blockade promotes antitumor responses against glioblastoma. In silico and immunohistochemical analyses revealed that the expression of ILT2 and its ligands HLA-A, -B, -C, and -E are highly expressed in patients with glioblastoma. Disruption of ILT2 with blocking monoclonal antibodies increased natural killer cell-mediated IFN-γ production and cytotoxicity against glioblastoma, partially reverting the immunosuppression linked to this malignancy. In addition, co-treatment with temozolomide strengthened the antitumor capacity of anti-ILT2-treated immune cells. Collectively, our results establish the basis for future studies regarding the clinical potential of ILT2 blockade alone or in combination regimens in glioblastoma.
Insights
Blocking the novel immune checkpoint ILT2 enhances antitumor responses in glioblastoma. This approach boosts natural killer cell activity and shows potential when combined with temozolomide for improved glioblastoma treatment.
Area of Science:
- Immunology
- Neuro-oncology
- Cancer immunotherapy
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis despite current therapies.
- Immune checkpoint inhibitors show promise in various cancers, but their efficacy in GBM requires further investigation.
- ILT2 (Immune Locus Transcript 2) is an immune checkpoint receptor that inhibits antitumor responses.
Purpose of the Study:
- To investigate the therapeutic potential of blocking ILT2 in glioblastoma.
- To evaluate the expression of ILT2 and its ligands in GBM tumors.
- To assess the impact of ILT2 blockade on immune cell activity and tumor cell killing.
Main Methods:
- In silico and immunohistochemical analyses to determine ILT2 and HLA ligand expression in GBM.
- In vitro studies using blocking monoclonal antibodies against ILT2.
- Assessment of natural killer (NK) cell-mediated cytotoxicity and Interferon-gamma (IFN-γ) production.
- Combination therapy studies with temozolomide.
Main Results:
- ILT2 and its ligands (HLA-A, -B, -C, -E) are highly expressed in glioblastoma patients.
- ILT2 blockade with monoclonal antibodies enhanced NK cell-mediated cytotoxicity and IFN-γ production against GBM cells.
- ILT2 blockade partially reversed the immunosuppressive tumor microenvironment.
- Combination therapy with temozolomide further augmented the antitumor effects.
Conclusions:
- ILT2 blockade demonstrates significant potential to enhance antitumor immunity in glioblastoma.
- Targeting ILT2 represents a promising strategy for novel glioblastoma therapies.
- Combination regimens involving ILT2 blockade may offer improved clinical outcomes for glioblastoma patients.
More Related Videos
12:55Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
Published on: February 16, 2015
11:15Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts
Published on: September 1, 2018
