决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Variable Expression of the Disialoganglioside GD2 in Breast Cancer Molecular Subtypes.
研究了 IHC(n = 568)和 IF(n = 503)检测的 GD2 表达与亚型及患者结局的关系。
双唾液酸神经节苷脂GD2是一种肿瘤相关抗原,可使神经母细胞瘤及其他实体瘤患者有机会接受靶向免疫疗法(抗GD2抗体、GD2 CAR T细胞)。本研究回顾性分析乳腺癌队列中的GD2表达,使用组织芯片开展免疫组化(IHC)和免疫荧光(IF),并评估其对生存的影响。研究分析IHC(n=568)及IF(n=503)所测GD2表达与乳腺癌亚型和患者结局的关系。568份IHC样本中50.2%、503份IF样本中69.8%为GD2阳性。管腔型肿瘤中GD2阳性比例最高;与其他亚型相比,三阴性乳腺癌(TNBC)GD2阳性病例显著较少。IF结果显示,HER2阳性乳腺癌GD2表达肿瘤比例显著低于管腔型肿瘤,IHC结果则无此差异。无论在总体队列还是各亚型中,IHC或IF测得的GD2表达均与无病生存或总生存无显著关联。不过,超过半数乳腺癌病例可检测到GD2表达,且在激素受体阳性肿瘤中最常见。鉴于表达比例较高,各亚型中GD2阳性的晚期乳腺癌患者均可能从靶向GD2的免疫疗法中获益;此类疗法目前正在临床试验中评估。
The disialoganglioside GD2 is a tumor-associated antigen that may allow for the application of targeted immunotherapies (anti-GD2 antibodies, GD2 CAR T cells) in patients with neuroblastoma and other solid tumors. We retrospectively investigated GD2 expression in a breast cancer cohort, using immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays (TMAs), and its impact on survival. GD2 expression on IHC ( n = 568) and IF ( n = 503) was investigated in relation to subtypes and patient outcome. Overall, 50.2% of the 568 IHC-assessed samples and 69.8% of the 503 IF-assessed samples were GD2-positive. The highest proportion of GD2-positive tumors was observed in luminal tumors. Significantly fewer GD2-positive cases were detected in triple-negative breast cancer (TNBC) compared with other subtypes. The proportion of GD2-expressing tumors were significantly lower in HER2-positive breast cancer in comparison with luminal tumors on IF staining (but not IHC). GD2 expression of IHC or IF was not significantly associated with disease-free or overall survival, in either the overall cohort or in individual subtypes. However, GD2 expression can be seen in more than 50% of breast cancer cases, with the highest frequency in hormone receptor-positive tumors. With this high expression frequency, patients with GD2-positive advanced breast cancer of all subtypes may benefit from GD2-targeting immunotherapies, which are currently subject to clinical testing.
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