免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Multi-modal molecular programs regulate melanoma cell state.
Multi-modal molecular programs regulate melanoma cell state.
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黑色素瘤细胞表现出不同的内在表型状态。在此,我们通过对68株高度注释的早期传代黑色素瘤细胞系进行全外显子、转录组、microRNA、长非编码RNA和DNA甲基化数据的多组学分析,并结合反相蛋白阵列数据,力求刻画这些状态的分子调控。我们证明,明确界定的癌细胞内在转录组程序在离体黑色素瘤细胞中得以维持,并在黑色素瘤肿瘤内高度保守,与肿瘤内不同的免疫特征相关,并与检查点抑制剂和过继性T细胞疗法疗效存在差异性相关。通过整合分析,我们证明黑色素瘤细胞内在程序受到高度复杂的多组学调控,为表型状态的分子维持提供了关键见解。这些发现对癌症生物学和新治疗策略的识别具有重要意义。此外,这些经过深度表征的细胞系将成为该领域未来研究的宝贵资源。
Melanoma cells display distinct intrinsic phenotypic states.
Here, we seek to characterize the molecular regulation of these states using multi-omic analyses of whole exome, transcriptome, microRNA, long non-coding RNA and DNA methylation data together with reverse-phase protein array data on a panel of 68 highly annotated early passage melanoma cell lines.
We demonstrate that clearly defined cancer cell intrinsic transcriptomic programs are maintained in melanoma cells ex vivo and remain highly conserved within melanoma tumors, are associated with distinct immune features within tumors, and differentially correlate with checkpoint inhibitor and adoptive T cell therapy efficacy. Through integrative analyses we demonstrate highly complex multi-omic regulation of melanoma cell intrinsic programs that provide key insights into the molecular maintenance of phenotypic states.
These findings have implications for cancer biology and the identification of new therapeutic strategies.
Further, these deeply characterized cell lines will serve as an invaluable resource for future research in the field.
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