Immunoglobulin-like transcript 2 blockade restores antitumor immune responses in glioblastoma.

Autor: Lorenzo-Herrero S; Department of Functional Biology, Immunology, Universidad de Oviedo, Oviedo, Spain.; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain., Sordo-Bahamonde C; Department of Functional Biology, Immunology, Universidad de Oviedo, Oviedo, Spain.; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain., Martínez-Pérez A; Department of Functional Biology, Immunology, Universidad de Oviedo, Oviedo, Spain.; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain., Corte-Torres MD; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.; Biobanco del Principado de Asturias, Oviedo, Spain., Fernández-Vega I; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.; Biobanco del Principado de Asturias, Oviedo, Spain.; Department of Pathology, Hospital Universitario Central de Asturias, Oviedo, Spain., Solís-Hernández MP; Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain., González S; Department of Functional Biology, Immunology, Universidad de Oviedo, Oviedo, Spain.; Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.
Jazyk: angličtina
Zdroj: Cancer science [Cancer Sci] 2023 Jan; Vol. 114 (1), pp. 48-62. Date of Electronic Publication: 2022 Sep 23.
DOI: 10.1111/cas.15575
Abstrakt: 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.
(© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
Databáze: MEDLINE
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