CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Genetic and Immunological Characterization of Brain Metastases from Solid Cancers.
Genetic and Immunological Characterization of Brain Metastases from Solid Cancers.
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转移性病灶中高 TMB 提示脑转移患者可能从免疫检查点抑制剂治疗中获益，TREML2 和 BTLA 是与不良预后相关的因素。活化的小胶质细胞可能是治疗脑转移的新靶点。
脑转移是癌症死亡的主要原因，也是一项临床难题。近年来，基于下一代测序等先进技术（如单细胞 RNA 测序）对脑转移病灶进行遗传学特征分析，已被用于开发新的有效疗法。本研究旨在探讨脑转移特异性生物标志物及相关预后因素。
在静冈癌症中心从九名癌症患者获取的原发癌病灶和转移癌病灶之间，比较了免疫反应相关基因和820个癌症相关基因的遗传图谱和表达水平。通过定量PCR分析了细胞因子和趋化因子标记基因。对同一批患者进行了T细胞受体（TCR）库分析。在生存分析中，利用了52名伴有脑转移的癌症患者的生存数据。
原发灶与转移灶驱动突变谱比较显示，两处病灶共享核心突变，转移灶中存在少量新突变。转移灶中检测到高肿瘤突变负荷（TMB）。火山图分析揭示了转移性肿瘤微环境的特异性特征，如癌症信号促进以及因免疫细胞浸润减少导致的免疫抑制。生存分析显示，三个基因——TREML2基因、活化小胶质细胞上的BTLA基因以及转移性肿瘤上的CERS2基因——是有力的预后因素。
The genetic profiles and expression levels of immune response-associated genes and 820 cancer-associated genes were compared between primary cancer lesions and metastatic cancer lesions obtained from nine cancer patients at the Shizuoka Cancer Center. Cytokine and chemokine marker genes were analyzed via quantitative PCR. T-cell receptor (TCR) repertoire profiling was performed for the same patients. For survival analysis, survival data of 52 cancer patients with brain metastases were utilized.
Comparison of driver mutation profiling between primary and metastatic lesions revealed shared core mutations in both lesions and a few new mutations in metastatic lesions. A high tumor mutation burden (TMB) was detected in metastatic lesions. Volcano plot analysis revealed specific features of the metastatic tumor microenvironment, such as cancer signaling promotion and immune suppression due to decreased immune cell infiltration. Survival analysis revealed that three genes, the TREML2 gene, the BTLA gene on activated microglia and the CERS2 gene on metastatic tumor, were potent prognostic factors.
High TMB in metastatic lesions indicates potential benefit from immune checkpoint inhibitor usage for brain metastasis and TREML2 and BTLA are factors associated with poor prognosis. Activated microglia may be novel targets for the treatment of brain metastasis.
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