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:Associations between BCL-2 expression and different histopathological prognostic factors in different molecular subtypes of invasive breast carcinoma of no special type.
BCL-2在IBC中的表达;NST根据癌症分子亚型的不同具有不同的预后影响。在HER2富集表型的癌症中,BCL-2表达是不良预后的标志物,而在激素受体阳性表型的癌症中,BCL-2表达具有较好的预后影响。
乳腺癌具有异质性,现有的预后分类器准确性有限,导致许多女性接受不必要的治疗。B细胞淋巴瘤2(BCL-2)是一种抗凋亡蛋白,已被提出作为不良预后的标志物,在大多数表达BCL-2的肿瘤类型中与治疗耐药相关。然而,在乳腺癌中,BCL-2表达被报道为有利的预后因素。本研究旨在描述在不同分子亚型的非特殊型浸润性乳腺癌(IBC;NST)中,BCL-2与其他众所周知的病理预后标志物之间的关联。
在128例诊断为IBC;NST的乳腺癌病例中,采用免疫组化(IHC)评估BCL-2表达以及雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER2)表达,并与其他病理因素进行比较,包括肿瘤大小、分级、TIL(肿瘤浸润淋巴细胞)(TILs)、淋巴血管侵犯(LVI)和淋巴结(LNd)转移。此外,我们分析了所有患者中BCL-2表达与两年内无复发生存期(RFS)之间的相关性。
我们发现,BCL-2 表达在不同分子亚型乳腺癌中与不同的病理预后因素相关。在 luminal A 型(即激素受体阳性和 HER2 阴性)和三阴性亚型中,肿瘤细胞中 BCL-2 的表达与肿瘤大小、肿瘤分级和 TILs 显著相关。在 luminal IBC;NST 患者中,BCL2 阳性表达带来了显著有利的两年生存。
BACKGROUND: Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to the unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL-2), an anti-apoptotic protein, has been proposed as a marker of poor prognosis, associated with resistance to therapy in most tumor types expressing BCL-2. In breast cancer, however, BCL-2 expression has been reported to be a favorable prognostic factor. This study aimed to describe the association between BCL-2 and other well-known pathological prognostic markers among different molecular sub-types of invasive breast carcinoma of no special type (IBC; NST). METHODS: BCL-2 expression, as well as that of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were immunohistochemically (IHC) evaluated and compared with other pathological factors, including tumor size, grade, tumor-infiltrating lymphocytes (TILs), lymph-vascular invasion (LVI), and lymph node (LNd) metastasis, in 128 breast cancer cases diagnosed with IBC; NST. Moreover, we analyzed the correlation between BCL-2 expression and relapse-free survival (RFS) in all patients over a two-year period. RESULTS: We found that BCL-2 expression had different pathological prognostic factor associations with different molecular subtypes of breast carcinoma. In the luminal A (i.e., hormonal receptor-positive and HER2-negative) and triple-negative subtypes, the expression of BCL-2 in tumor cells was significantly associated with tumor size, tumor grade, and TILs. BCL2-positive expression in luminal IBC; NST patients resulted in a significantly favorable two-year survival. CONCLUSION: BCL-2 expression in IBC; NST has different prognostic effects depending on the molecular subtype of the cancer. In cancers with a HER2-enriched phenotype, BCL-2 expression was a marker of poor prognosis, while in cancers with a hormone receptor-positive phenotype, BCL-2 expression had a better prognostic impact.
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