三阴性乳腺癌间质中PD-L1强表达与其较良好的无病生存期DFS相关

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  译:爱水的鱼
  三阴性乳腺癌(TNBC)是乳腺癌常见的分子亚型之一,侵袭性较强,恶性度高的亚型,目前还没有针对TNBC的靶向治疗药物被批准。作者研究了程序性细胞死亡蛋白1(PD-1)及其配体(PD-L1)在三阴性乳腺癌中的表达情况。该研究分析了2004年至2013年间136例未行新辅助治疗的三阴性乳腺癌标本间质免疫细胞PD-1的表达以及间质或肿瘤PD-L1的染色,并采用H积分(染色百分比×强度)对染色结果进行评分。同时对三阴性乳腺癌进行了Nottingham组织学分级、淋巴血管浸润(LVI)、核分裂像和肿瘤浸润性淋巴细胞(TIL)的评估。肿瘤直径、淋巴结转移情况、Ki-67评分、转移、总生存期(OS)和无病生存期(DFS)等临床病理情况采集于医疗记录中。结果显示136例三阴性乳腺癌中,69例(51%)有PD-L1表达,其中35例(26%)PD-L1的H积分在5分或以上;117例(86%)有PD-1表达,其中68例(50%)PD-1的H积分在5分或以上)。单因素分析中肿瘤直径大小、淋巴血管浸润与较差的OS和DFS显着相关,肿瘤浸润性淋巴细胞和淋巴血管浸润与转移呈显着性相关。多因素分析显示间质PD-L1表达与更好的DFS显着性相关。PD-1表达与肿瘤转移、总生存期和无病生存期均无关。研究结果提示PD-L1更多表达于三阴性乳腺癌中,并与三阴性乳腺癌更好的无病生存期密切相关。
  延伸阅读:
  TNBC:三阴性乳腺癌是指免疫组织化学检查结果为雌激素受体(ER)、孕激素受体(PR)和原癌基因HER-2均为阴性的乳腺癌。占所有乳腺癌病理类型的10.0%~20.8%,具有特殊的生物学行为和临床病理特征,预后较其他类型差。
  PD-1:PD-1(programmed death 1)程序性死亡受体1,是一种重要的免疫抑制分子。为CD28超家族成员,其最初是从凋亡的小鼠T细胞杂交瘤2B4.11克隆出来。以PD-1为靶点的免疫调节对抗肿瘤、抗感染、抗自身免疫性疾病及器官移植存活等均有重要的意义。其配体PD-L1也可作为靶点,相应的抗体也可以起到相同的作用。
  PD-L1:PD-L1(programmed cell death-Ligand 1) 程序性死亡受体-配体1,又称作CD274或B7-H1,是一种I型跨膜蛋白,参与细胞的和体液免疫应答的调节。PD-L1主要表达在抗原呈递细胞、活化T细胞和B细胞、胎盘和一些肿瘤如黑色素瘤、弥漫型大B细胞淋巴瘤、肺癌、结直肠癌等。
  来源:
  《Stromal PD-L1 Expression Is Associated With Better Disease-Free Survival in Triple-Negative Breast Cancer》 Am J Clin Pathol. 2016 Oct;146(4):496-502. doi: 10.1093/ajcp/aqw134. DOI: 10.1093/ajcp/aqw134  PMID: 27686176  [PubMed - in process]
  摘要原文:
  OBJECTIVES: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, and there is no approved targeted therapy. We studied the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in TNBC. METHODS: Full-face sections from 136 TNBC cases without neoadjuvant therapy between 2004 and 2013 were stained and evaluated for immune cell PD-1 staining and stromal or tumoral PD-L1 staining using the H-score (staining percentage × intensity). Nottingham histologic grade, lymphovascular invasion (LVI), mitotic count, and tumor-infiltrating lymphocytes (TILs) were evaluated. Tumor size,lymph node status, Ki-67 score, metastasis, overall survival (OS), and disease-free survival (DFS) were retrieved from medical records.RESULTS: Of the 136 TNBC cases, 69 (51%) had any PD-L1 staining and 35 (26%) had PD-L1 staining with an H-score of?5 or more; 117 (86%) had any PD-1 staining and 68 (50%) had PD-1 staining with an H-score of 5 or more. Tumor size and LVI were significantly associated with worse OS and DFS, and TILs and LVI were significantly associated with metastasis in univariate analysis. Stromal PD-L1 expression was significantly associated with better DFS in multivariate analysis. PD-1 expression was not associated with DFS, OS, or metastasis.CONCLUSIONS: PD-L1 expression is seen in a high proportion of TNBCs and associated with better DFS.
 
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