Comprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of nasopharyngeal carcinoma.
Comprehensive single-cell sequencing reveals the stromal dynamics and tumor-specific characteristics in the microenvironment of nasopharyngeal carcinoma.
复制标题
DOI：
10.1038/s41467-021-21795-z
复制
发表时间：
2021-03-09
影响因子：
16.6
通讯作者：
Guan XY
中科院分区：
文献类型：
--
作者：
Gong L;Kwong DL;Dai W;Wu P;Li S;Yan Q;Zhang Y;Zhang B;Fang X;Liu L;Luo M;Liu B;Chow LK;Chen Q;Huang J;Lee VH;Lam KO;Lo AW;Chen Z;Wang Y;Lee AW;Guan XY
鼻咽癌（NPC）的肿瘤微环境（TME）包含异质性且动态变化的基质细胞群。全面了解这种肿瘤特异性的生态系统对于加强癌症诊断、治疗和预后是必要的。然而，基于大量RNA测序的近期进展仍不足以构建鼻咽癌中浸润性基质细胞的深度图谱。在此，我们对14名患者的66,627个细胞应用单细胞RNA测序，并结合T细胞和B细胞的克隆型鉴定。我们基于基因图谱识别并描述了5个主要的基质细胞群和36个不同的亚群。通过与非恶性微环境中的浸润细胞进行比较，我们报道了肿瘤微环境中极具代表性的特征，包括表型丰度、基因改变、免疫动态、克隆扩增、发育轨迹以及分子相互作用，这些都对患者预后和治疗结果产生深远影响。关键发现进一步在两个单细胞RNA测序队列和两个大量RNA测序队列中得到独立验证。在本研究中，我们揭示了鼻咽癌特异性特征与无进展生存期之间的相关性。总之，这些数据有助于理解鼻咽癌患者的基质细胞图谱和免疫动态，并为肿瘤微环境中预后生物标志物和治疗靶点的开发提供更深入的见解。
肿瘤微环境会影响患者对治疗的生存反应。在此，作者使用单细胞测序来研究鼻咽癌的微环境，并在5个基质细胞群中识别可能影响患者生存的肿瘤特异性特征。
The tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this tumor-specific ecosystem is necessary to enhance cancer diagnosis, therapeutics, and prognosis. However, recent advances based on bulk RNA sequencing remain insufficient to construct an in-depth landscape of infiltrating stromal cells in NPC. Here we apply single-cell RNA sequencing to 66,627 cells from 14 patients, integrated with clonotype identification on T and B cells. We identify and characterize five major stromal clusters and 36 distinct subpopulations based on genetic profiling. By comparing with the infiltrating cells in the non-malignant microenvironment, we report highly representative features in the TME, including phenotypic abundance, genetic alternations, immune dynamics, clonal expansion, developmental trajectory, and molecular interactions that profoundly influence patient prognosis and therapeutic outcome. The key findings are further independently validated in two single-cell RNA sequencing cohorts and two bulk RNA-sequencing cohorts. In the present study, we reveal the correlation between NPC-specific characteristics and progression-free survival. Together, these data facilitate the understanding of the stromal landscape and immune dynamics in NPC patients and provides deeper insights into the development of prognostic biomarkers and therapeutic targets in the TME. The tumor microenvironment can influence patient survival response to therapy. Here, the authors used single-cell sequencing to investigate the microenvironment of nasopharyngeal cancer and identify tumor-specific signatures in five stromal clusters of cells that may influence patient survival.
登录
查看更多内容
影响因子：
64.8
作者：
Helmink BA;Reddy SM;Gao J;Zhang S;Basar R;Thakur R;Yizhak K;Sade-Feldman M;Blando J;Han G;Gopalakrishnan V;Xi Y;Zhao H;Amaria RN;Tawbi HA;Cogdill AP;Liu W;LeBleu VS;Kugeratski FG;Patel S;Davies MA;Hwu P;Lee JE;Gershenwald JE;Lucci A;Arora R;Woodman S;Keung EZ;Gaudreau PO;Reuben A;Spencer CN;Burton EM;Haydu LE;Lazar AJ;Zapassodi R;Hudgens CW;Ledesma DA;Ong S;Bailey M;Warren S;Rao D;Krijgsman O;Rozeman EA;Peeper D;Blank CU;Schumacher TN;Butterfield LH;Zelazowska MA;McBride KM;Kalluri R;Allison J;Petitprez F;Fridman WH;Sautès-Fridman C;Hacohen N;Rezvani K;Sharma P;Tetzlaff MT;Wang L;Wargo JA
通讯作者：
Wargo JA
影响因子：
45.3
作者：
Hsu, Chiun;Lee, Se-Hoon;Hansen, Aaron R.
通讯作者：
Hansen, Aaron R.
影响因子：
64.8
作者：
Khan, Omar;Giles, Josephine R.;Wherry, E. John
通讯作者：
Wherry, E. John
影响因子：
7.3
作者：
Chávez-Galán L;Olleros ML;Vesin D;Garcia I
通讯作者：
Garcia I
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF