肿瘤细胞治疗研究
英文原题：Expression features of targets for anti-glioma CAR-T cell immunotherapy.
抗胶质瘤 CAR-T 靶点在不同胶质瘤亚型中表达异质、肿瘤覆盖情况不同，并与胶质瘤的恶性或免疫表型密切相关。
目的：研究常见抗胶质瘤CAR-T靶点（B7H3、CSPG4、EGFRvIII、HER2和IL-13Rα2）在不同级别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（包括免疫逃逸、干性、抗原呈递和肿瘤血管生成）之间的关联。 方法：对胶质瘤组织进行Opal多重免疫荧光染色，以检测靶点及相关表型生物标志物的表达。 结果：不同胶质瘤亚型之间CAR-T靶点表达存在高度差异。在各胶质瘤亚型中，GBM所检测靶点的表达水平均最高。所有胶质瘤病例中，CSPG4是最常见的靶点，覆盖超过84%的病例；其次为B7H3，覆盖超过64%。在GBM中，B7H3覆盖率最高，为94%；在少突胶质细胞瘤和星形细胞瘤中，CSPG4最常见，覆盖率分别为94%和80%。双靶点或三靶点联合策略显著扩大了各胶质瘤病例中的肿瘤覆盖范围，也提高了肿瘤内肿瘤细胞覆盖率。与靶点阴性细胞群相比，所有靶点阳性细胞（EGFRvIII阳性细胞除外）中PD-L1表达均显著富集；CSPG4阳性或IL-13Rα2阳性细胞中CD133表达较高，而B7H3阳性细胞中CD31表达升高。 结论：抗胶质瘤CAR-T靶点在不同胶质瘤亚型中的表达及肿瘤覆盖范围存在异质性，并与胶质瘤恶性或免疫表型密切相关。
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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