Expression features of targets for anti-glioma CAR-T cell immunotherapy.

IF 3.2 2区 医学 Q2 CLINICAL NEUROLOGY Journal of Neuro-Oncology Pub Date : 2024-10-28 DOI:10.1007/s11060-024-04855-4
Peng Zhang, Chunzhao Li, Yi Wang, Xiaohan Chi, Tai Sun, Qianhe Zhang, Yang Zhang, Nan Ji
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Abstract

Objective: To investigate the expression features of common anti-glioma CAR-T targets (B7H3, CSPG4, EGFRv III, HER2 and IL-13Ra2) in gliomas with different grades and molecular subtypes, and explore the association of target expression with glioma malignant or immune phenotypes including immune evasion, stemness, antigen presentation, and tumor angiogenesis.

Methods: Opal™ Multiplex immunofluorescence staining was performed on glioma tissues to detect the expression of targets, and biomarkers related to the phenotypes.

Results: High variety of CAR-T target expression among glioma subtypes was observed. GBMs exhibited the highest expression level of all the examined targets among glioma subtypes. In all glioma cases, CSPG4 was the most prevalent target covering over 84% glioma cases, followed by B7H3 at over 64%. B7H3 exhibited the highest coverage (94%) in GBMs while CSPG4 was the most popular target in both oligodendrogliomas and astrocytomas, covering 94% and 80% cases, respectively. Bi or tri-target combination strategies markedly expanded the tumor coverage across glioma cases while increased tumor-cell coverage within tumor. PD-L1 expression was significantly enriched in all the target-positive cells (except the EGFRvIII+ cells); CD133 expression was higher in the CSPG4+ or IL-13Ra2+ cells, and CD31 elevated in the B7H3+ cells, as compared with their negative cell populations.

Conclusion: Anti-glioma CAR-T targets have heterogenous expression and distinct tumor coverage among glioma subtypes, and closely correlate with glioma malignant or immune phenotypes.

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抗胶质瘤 CAR-T 细胞免疫疗法靶点的表达特征。
目的研究常见抗胶质瘤CAR-T靶点(B7H3、CSPG4、表皮生长因子受体v III、HER2和IL-13Ra2)在不同分级和分子亚型胶质瘤中的表达特征,并探讨靶点表达与胶质瘤恶性或免疫表型(包括免疫逃避、干性、抗原提呈和肿瘤血管生成)的相关性:方法:对胶质瘤组织进行Opal™多重免疫荧光染色,检测靶点的表达以及与表型相关的生物标记物:结果:观察到胶质瘤亚型中CAR-T靶点表达的多样性。在胶质瘤亚型中,GBM 在所有检测靶点中的表达水平最高。在所有胶质瘤病例中,CSPG4是最普遍的靶点,覆盖了超过84%的胶质瘤病例,其次是B7H3,覆盖率超过64%。B7H3在GBM中的覆盖率最高(94%),而CSPG4则是少突胶质瘤和星形细胞瘤中最流行的靶点,覆盖率分别为94%和80%。双靶点或三靶点组合策略明显扩大了胶质瘤病例的肿瘤覆盖范围,同时增加了肿瘤内肿瘤细胞的覆盖范围。与阴性细胞群相比,PD-L1在所有靶点阳性细胞(表皮生长因子受体vIII+细胞除外)中表达明显丰富;CD133在CSPG4+或IL-13Ra2+细胞中表达较高,CD31在B7H3+细胞中升高:结论:抗胶质瘤CAR-T靶点在胶质瘤亚型中具有异质性表达和不同的肿瘤覆盖率,并与胶质瘤的恶性或免疫表型密切相关。
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来源期刊
Journal of Neuro-Oncology
Journal of Neuro-Oncology 医学-临床神经学
CiteScore
6.60
自引率
7.70%
发文量
277
审稿时长
3.3 months
期刊介绍: The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.
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