基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
过继性自然杀伤(NK)细胞疗法是治疗三阴性乳腺癌的一种有前景的策略,但其疗效往往受到瘤内持久性差以及在免疫抑制性肿瘤微环境中功能耗竭的限制。
英文原题:NSG2: a promising prognostic marker shaping the immune landscape of breast cancer.
NSG2: a promising prognostic marker shaping the immune landscape of breast cancer.
NSG2似乎是BC免疫微环境的重要组成部分,可能作为一个重要的预后标志物。
乳腺癌(BC)仍然是全球重要的健康问题,也是女性最常见的死亡原因。加深对生物标志物的理解可能大大改善该疾病的诊断和治疗方法。
我们回顾性评估了228例BC病例的肿瘤样本和51例正常样本,以及相关临床数据。通过生物信息学和多重免疫组化评估了神经元囊泡运输相关蛋白2(NSG2)的表达。研究了NSG2表达、肿瘤浸润免疫细胞(TIICs)、免疫检查点与临床结局之间的关联。
NSG2存在于乳腺癌细胞和邻近的基质细胞中。癌细胞中NSG2表达升高与更大的肿瘤体积、远处转移和更晚的临床分期相关。Kaplan-Meier生存分析和多因素分析确定,癌细胞和基质细胞中的NSG2表达均为乳腺癌生存的独立预后因素。癌细胞和基质细胞中NSG2水平升高与基质区域中CD4+ T细胞、CD8+ T细胞和Lamp3+树突状细胞浸润增加相关(P < 0.05)。相反,基质中NSG2的表达与CD20+ B细胞呈负相关(P < 0.05)。此外,NSG2表达被发现与CTLA-4水平相关(P < 0.05)。
BACKGROUND: Breast cancer (BC) remains a significant health issue globally and most common cause of mortality in women. Enhancing our understanding on biomarkers may greatly improve both diagnostic and therapeutic approaches to this disease. METHODS: We retrospectively assessed tumor samples from 228 BC cases and 51 normal samples, alongside relevant clinical data. Neuronal vesicle trafficking associated 2(NSG2) expression was evaluated through bioinformatics and multiplex immunohistochemistry. Associations between NSG2 expression, tumor-infiltrating immune cells (TIICs), immune checkpoints, and clinical outcomes were investigated. RESULTS: NSG2 was present in both breast cancer cells and adjacent stromal cells. Increased NSG2 expression in cancer cells correlated with greater tumor size, distant metastasis, and more advanced clinical stages. Kaplan-Meier survival and multivariate analyses identified NSG2 expression in both cancer and stromal cells as an independent prognostic factor for breast cancer survival. Elevated NSG2 levels both in cancer and stroma cells were linked to increased CD4+ T, CD8+ T, and Lamp3+ dendritic cells infiltration in stromal regions ( P < 0.05). Conversely, the expression of NSG2 in the stroma was negatively correlated with CD20+ B cells ( P < 0.05). Additionally, NSG2 expression was found to be associated with CTLA-4 levels ( P < 0.05). CONCLUSION: NSG2 seems to be a significant component of the BC immune microenvironment and may serve as an important prognostic marker.
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