下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Relationship between Aldehyde Dehydrogenase, PD-L1 and Tumor-Infiltrating Lymphocytes with Pathologic Response and Survival in Breast Cancer.
共分析75例患者(42.7%为TN肿瘤,57.3%为HER2+肿瘤)。
醛脱氢酶1A1(ALDH1A1)是一种与乳腺癌(BC)临床结局相关的癌症干细胞(CSC)标志物。本研究的目的是分析三阴性(TN)和人表皮生长因子受体2阳性(HER2+)BC肿瘤中ALDH1A1、程序性死亡配体1(PD-L1)与TIL(肿瘤浸润淋巴细胞)(TILs)之间的关系,及其与临床病理特征和结局的关联。本研究开展了一项回顾性历史队列研究,纳入接受新辅助化疗的早期或局部晚期BC患者。采用免疫组织化学方法评估ALDH1A1、PD-L1表达及TILs。共分析75例患者(42.7%为TN肿瘤,57.3%为HER2+肿瘤)。ALDH1A1+与HTILs(p = 0.005)和PD-L1+肿瘤(p = 0.004)相关。ALDH1A1+肿瘤表现出更高的CD3+(p = 0.008)、CD4+(p = 0.005)、CD8+(p = 0.003)和CD20+(p = 0.006)TILs。ALDH1A1+(p = 0.018)、PD-L1+(p = 0.004)和HTILs(p < 0.001)与更小的肿瘤相关。ALDH1A1+与病理完全缓解(pCR)相关(p = 0.048)。在随访结束时(54.4 [38.3−87.6]个月),47例患者(62.7%)仍无病生存,20例(26.7%)已死亡。HTILs与改善的无病生存期相关(p = 0.027)。ALDH1A1+与PD-L1+和HITLs相关,这可能与新辅助治疗中更高的pCR率相关。
Aldehyde dehydrogenase 1A1 (ALDH1A1) is a cancer stem cell (CSC) marker related to clinical outcomes in breast cancer (BC). The aim of this study was to analyze the relationship between ALDH1A1, programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in triple negative (TN) and human epidermal growth factor receptor 2-positive (HER2+) BC tumors, and its association with clinicopathological characteristics and outcomes. A retrospective, historical cohort study of patients diagnosed with early or locally advanced BC treated with neoadjuvant chemotherapy was conducted. ALDH1A1, PD-L1 expression and TILs were assessed using immunohistochemistry. A total of 75 patients were analyzed (42.7% TN, 57.3% HER2+ tumors). ALDH1A1+ was related to HTILs (p = 0.005) and PD-L1+ tumors (p = 0.004). ALDH1A1+ tumors presented higher CD3+ (p = 0.008), CD4+ (p = 0.005), CD8+ (p = 0.003) and CD20+ (p = 0.006) TILs. ALDH1A1+ (p = 0.018), PD-L1+ (p = 0.004) and HTILs (p < 0.001) were related to smaller tumors. ALDH1A1+ was related to pathologic complete response (pCR) (p = 0.048). At the end of the follow-up (54.4 [38.3−87.6] months), 47 patients (62.7%) remained disease-free, and 20 (26.7%) had died. HTILs were related to improved disease-free survival (p = 0.027). ALDH1A1+ was related to PD-L1+ and HITLs, that might be related to higher pCR rates with neoadjuvant therapy.
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