Immunoglobulin-like transcript 2 blockade restores antitumor immune responses in glioblastoma,Cancer Science

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Immunoglobulin-like transcript 2 blockade restores antitumor immune responses in glioblastoma
Cancer Science ( IF 4.5 ) Pub Date : 2022-09-09 , DOI: 10.1111/cas.15575
Seila Lorenzo-Herrero _{1,

2,

3} , Christian Sordo-Bahamonde _{1,

2,

3} , Alejandra Martínez-Pérez _{1,

2,

3} , Mª Daniela Corte-Torres _{3,

4} , Iván Fernández-Vega _{2,

3,

4,

5} , Mª Pilar Solís-Hernández ₆ , Segundo González _{1,

2,

3}

Affiliation

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.

中文翻译：

免疫球蛋白样转录物 2 阻断可恢复胶质母细胞瘤的抗肿瘤免疫反应

胶质母细胞瘤是最常见的原发性脑肿瘤。尽管对胶质母细胞瘤患者进行了多模式治疗，但存活率非常低，这凸显了对改善患者预后的新疗法的需求。免疫检查点阻断策略在无数肿瘤中取得了可喜的成果，一些研究报告了其在临床前水平上对胶质母细胞瘤的疗效。ILT2 是一种新型免疫检查点，通过与经典和非经典 HLA I 类分子相互作用发挥抑制作用。在此，我们报告 ILT2 阻断促进针对胶质母细胞瘤的抗肿瘤反应。计算机和免疫组织化学分析表明，胶质母细胞瘤患者中 ILT2 及其配体 HLA-A、-B、-C 和 -E 的表达高度表达。用阻断性单克隆抗体破坏 ILT2 会增加自然杀伤细胞介导的 IFN-γ 产生和针对胶质母细胞瘤的细胞毒性，部分恢复与这种恶性肿瘤相关的免疫抑制。此外，与替莫唑胺联合治疗可增强经抗 ILT2 处理的免疫细胞的抗肿瘤能力。总的来说，我们的结果为未来研究 ILT2 单独或联合治疗胶质母细胞瘤的临床潜力奠定了基础。

更新日期：2022-09-09

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