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:Combining Analysis of Tumor-infiltrating Lymphocytes (TIL) and PD-L1 Refined the Prognostication of Breast Cancer Subtypes.
数据提示,联合分析sTIL与PD-L1-IC表达可细化乳腺癌亚型的预后判断。TIL和PD-L1-IC高表达的病例似乎更具免疫活性。
PD-L1已被用作生物标志物,用于筛选适合接受PD-1/PD-L1抑制剂治疗的患者。
在本研究中,我们评估了与PD-L1表达相关的乳腺癌临床病理特征,及其与其他免疫成分的关系和预后意义。
本队列共纳入1752例病例。肿瘤浸润免疫细胞PD-L1表达(PD-L1-IC)和肿瘤细胞PD-L1表达(PD-L1-TC)分别在34.2%和10.1%的病例中检出,且二者与更高的肿瘤分级、形态学大汗腺特征、坏死存在及更高的间质TIL(肿瘤浸润淋巴细胞)(sTIL)呈正相关。PD-L1-IC与PD-L1-TC表达相互呈正相关,且二者均与雌激素受体和孕激素受体呈负相关,与Ki67、HER2、EGFR、p63和p-cadherin呈正相关。在生存分析中,PD-L1-IC表达与HER2过表达(HER2-OE)癌和高分级luminal B癌中更好的无病生存期(DFS)和乳腺癌特异性生存期(BCSS)相关。在三阴性乳腺癌(TNBC)和HER2-OE癌中,与sTIL低且PD-L1-IC阴性病例相比,sTIL高病例显示出显著更好的DFS,且不依赖于PD-L1-IC状态。sTIL低且PD-L1-IC阳性病例在HER2-OE癌中也显示出更好的DFS。在高分级luminal B癌中,sTIL高且PD-L1-IC阳性病例显示出最佳的BCSS。
BACKGROUND: PD-L1 has been used as a biomarker to select patients for treatment of PD-1/PD-L1 inhibitors. MATERIALS AND METHODS: In this study, we assessed the clinicopathological features of breast cancers that are associated with PD-L1 expression, as well as its relationship with other immune components and its prognostic significance. RESULTS: Totally 1752 cases were included in this cohort. PD-L1 expression in tumor-infiltrating immune cells (PD-L1-IC) expression and in tumor cells (PD-L1-TC) expression were identified in 34.2% and 10.1% of cases, respectively, and they showed a positive correlation with higher tumor grade, morphological apocrine features, presence of necrosis, and higher stromal tumor-infiltrating lymphocytes (sTIL). PD-L1-IC and PD-L1-TC expression correlated positively with each other, and both of them were negatively associated with estrogen receptor and progesterone receptor and positively associated with Ki67, HER2, EGFR, p63, and p-cadherin. In survival analysis, PD-L1-IC expression was associated with better disease-free survival (DFS) and breast cancer-specific survival (BCSS) in HER2-overexpressed (HER2-OE) cancers and high-grade luminal B cancers. In triple-negative breast cancers (TNBC) and HER2-OE cancers, compared with sTIL low PD-L1-IC negative cases, sTIL high cases showed significantly better DFS independent of PD-L1-IC status. sTIL low PD-L1-IC positive cases also demonstrated a better DFS in HER2-OE cancers. In high-grade luminal B cancers, sTIL high PD-L1-IC positive cases showed the best BCSS. CONCLUSION: The data suggested that the combining analysis of sTIL and PD-L1-IC expression refined the prognostication of breast cancer subtypes. Cases with high TIL and PD-LI-IC expression appear to be more immune active.
MEMBER ACCOUNT
登录成功会直接打开下一页。