CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
我们的工作确立了CD81作为连接放射抵抗与免疫逃逸的关键桥梁,其通过维持GBM中CD274的丰度发挥作用,并突显CD81作为优化放射免疫治疗的有前景的治疗靶点。
英文原题:Clinical Relevance of Tumour-Infiltrating Immune Cells in HER2-Negative Breast Cancer Treated with Neoadjuvant Therapy.
回顾性收集了118例患者的肿瘤组织和外周血样本,并评估了sTILs。
目前,HER2阴性乳腺癌(BC)的治疗反应无法准确预测。测量间质TIL(肿瘤浸润淋巴细胞)(sTILs)和肿瘤微环境介质,并表征肿瘤浸润免疫细胞(TIICs),可能改善新辅助治疗中的治疗反应。回顾性收集了118例患者的肿瘤组织和外周血样本,并评估了sTILs。通过流式细胞术测定循环外泌体和髓源性抑制细胞。通过免疫组织化学评估TIICs标志物(CD4、CD8、CD20、CD1a和CD68)。高sTILs与病理完全缓解(pCR;p = 0.048)和无事件生存期(EFS;p = 0.027)显著相关。高CD68细胞与三阴性(TN)BC的pCR显著相关(p = 0.027),高CD1a细胞与luminal-B型BC的EFS显著相关(p = 0.012)。TIICs的聚类分析揭示了两组具有不同免疫模式和临床结局的肿瘤(C1和C2)。基于临床病理变量开发了一种免疫评分,以识别高风险(C1)或低风险(C2)患者。此外,聚类分析还揭示了luminal-B型和TNBC各自的两组肿瘤。我们的发现支持sTILs与pCR的关联,并显示在HER2阴性BC患者的一个亚群中存在免疫学组分。我们的免疫评分可能有助于未来的治疗升级或降级。
Currently, therapy response cannot be accurately predicted in HER2-negative breast cancer (BC). Measuring stromal tumour-infiltrating lymphocytes (sTILs) and mediators of the tumour microenvironment and characterizing tumour-infiltrating immune cells (TIICs) may improve treatment response in the neoadjuvant setting. Tumour tissue and peripheral blood samples were retrospectively collected from 118 patients, and sTILs were evaluated. Circulating exosomes and myeloid-derived suppressor cells were determined by flow cytometry. TIICs markers (CD4, CD8, CD20, CD1a, and CD68) were assessed immunohistochemically. High sTILs were significantly associated with pathological complete response (pCR; p = 0.048) and event-free survival (EFS; p = 0.027). High-CD68 cells were significantly associated with pCR in triple-negative (TN, p = 0.027) and high-CD1a cells with EFS in luminal-B ( p = 0.012) BC. Cluster analyses of TIICs revealed two groups of tumours (C1 and C2) that had different immune patterns and clinical outcomes. An immunoscore based on clinicopathological variables was developed to identify high risk (C1) or low-risk (C2) patients. Additionally, cluster analyses revealed two groups of tumours for both luminal-B and TNBC. Our findings support the association of sTILs with pCR and show an immunological component in a subset of patients with HER2-negative BC. Our immunoscore may be useful for future escalation or de-escalation treatments.
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