Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma
Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma
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单细胞RNA测序证实转移性肺腺癌的分子和细胞重编程
DOI：
10.1038/s41467-020-16164-1
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发表时间：
2020-05-08
影响因子：
16.6
通讯作者：
Lee, Hae-Ock
中科院分区：
文献类型：
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作者：
Kim, Nayoung;Kim, Hong Kwan;Lee, Hae-Ock
晚期转移性癌症是最大的临床挑战，可能表现出不同于早期癌症的分子和细胞特征。在此，我们展示了转移性肺腺癌的单细胞转录组谱，转移性肺腺癌是所有病例中40%以上在IV期诊断出的最常见的组织学肺癌类型。从44例正常组织或早期到转移期癌症患者的208,506个细胞中，我们发现了一种偏离正常分化轨迹并主导转移期的癌细胞亚型。在所有阶段，基质和免疫细胞动力学揭示了本体学和功能的变化，创造了促肿瘤和免疫抑制的微环境。正常的常驻骨髓细胞群逐渐被单核细胞来源的巨噬细胞和树突状细胞所取代，同时t细胞衰竭。这项广泛的单细胞分析增强了我们对转移性肺癌分子和细胞动力学的理解，并揭示了癌症-微环境相互作用中潜在的诊断和治疗靶点。了解导致肺腺癌转移的机制对于确定新的治疗方法非常重要。在这里，作者使用单细胞测序记录了人肺腺癌转录组的变化，并将癌细胞特征与免疫细胞动力学联系起来。
Advanced metastatic cancer poses utmost clinical challenges and may present molecular and cellular features distinct from an early-stage cancer. Herein, we present single-cell transcriptome profiling of metastatic lung adenocarcinoma, the most prevalent histological lung cancer type diagnosed at stage IV in over 40% of all cases. From 208,506 cells populating the normal tissues or early to metastatic stage cancer in 44 patients, we identify a cancer cell subtype deviating from the normal differentiation trajectory and dominating the metastatic stage. In all stages, the stromal and immune cell dynamics reveal ontological and functional changes that create a pro-tumoral and immunosuppressive microenvironment. Normal resident myeloid cell populations are gradually replaced with monocyte-derived macrophages and dendritic cells, along with T-cell exhaustion. This extensive single-cell analysis enhances our understanding of molecular and cellular dynamics in metastatic lung cancer and reveals potential diagnostic and therapeutic targets in cancer-microenvironment interactions. Understanding the mechanisms that lead to lung adenocarcinoma metastasis is important for identifying new therapeutics. Here, the authors document the changes in the transcriptome of human lung adenocarcinoma using single-cell sequencing and link cancer cell signatures to immune cell dynamics.