不可逆电穿孔增强 CAR-T 细胞对实体瘤的浸润与选择性癌细胞裂解
Irreversible Electroporation Enhances Solid Tumor Infiltration and Selective Cancer Cell Lysis by CAR T Cells.
通过利用一种双用途转化策略——直接的癌细胞靶向细胞毒性和增强的 CAR-T 细胞浸润——sIRE 能够减轻肿瘤负荷,同时保持并增强 CAR-T 细胞功能。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Epithelioid Pleural Mesothelioma Is Characterized by Tertiary Lymphoid Structures in Long Survivors: Results from the MATCH Study.
Epithelioid Pleural Mesothelioma Is Characterized by Tertiary Lymphoid Structures in Long Survivors: Results from the MATCH Study.
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胸膜间皮瘤(PM)是一种侵袭性肿瘤,治疗选择很少。尽管上皮样PM(ePM)患者的生存期长于非上皮样PM(non-ePM),但在ePM中观察到肿瘤反应的异质性。肿瘤免疫微环境(TIME)在PM发生和进展中的作用目前被认为是一种有前景的生物标志物。少数研究使用了与TIME评估相关的高通量技术以及形态学和临床数据。
本研究旨在识别可能预测预后的不同形态学、免疫组化和转录谱。研究招募了一个由129例未接受化疗的PM患者组成的回顾性多中心队列。组织切片由专科病理学家审阅,以进行组织学类型分类以及TIL(肿瘤浸润淋巴细胞)(TILs)和淋巴聚集或三级淋巴结构(TLS)的免疫表型分析。ePM(n = 99)生存者进一步分为长期生存者(>36个月)或短期生存者(<12个月)。对69份样本的一个子集进行了RNAseq。在长期和短期ePM生存者中发现了不同的转录谱。与短期ePM生存者相比,长期ePM生存者中检测到炎症背景,伴有更高数量的B淋巴细胞和TLS形成的普遍存在。这些结果提示,B细胞浸润可能在调节疾病侵袭性方面具有重要作用,为新的免疫治疗方法开辟了途径。
Pleural mesothelioma (PM) is an aggressive tumor with few therapeutic options. Although patients with epithelioid PM (ePM) survive longer than non-epithelioid PM (non-ePM), heterogeneity of tumor response in ePM is observed. The role of the tumor immune microenvironment (TIME) in the development and progression of PM is currently considered a promising biomarker. A few studies have used high-throughput technologies correlated with TIME evaluation and morphologic and clinical data.
This study aimed to identify different morphological, immunohistochemical, and transcriptional profiles that could potentially predict the outcome. A retrospective multicenter cohort of 129 chemonaive PM patients was recruited. Tissue slides were reviewed by dedicated pathologists for histotype classification and immunophenotype of tumor-infiltrating lymphocytes (TILs) and lymphoid aggregates or tertiary lymphoid structures (TLS). ePM (n = 99) survivors were further classified into long (>36 months) or short (<12 months) survivors.
RNAseq was performed on a subset of 69 samples. Distinct transcriptional profiling in long and short ePM survivors was found. An inflammatory background with a higher number of B lymphocytes and a prevalence of TLS formations were detected in long compared to short ePM survivors. These results suggest that B cell infiltration could be important in modulating disease aggressiveness, opening a pathway for novel immunotherapeutic approaches.
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