Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer
Fengying Wu,Jue Fan,Yayi He,Anwen Xiong,Jia Yu,Yixin Li,Yan Zhang,Wencheng Zhao,Fei Zhou,Wei Li,Jie Zhang,Xiaosheng Zhang,Meng Qiao,Guanghui Gao,Shanhao Chen,Xiaoxia Chen,Xuefei Li,Likun Hou,Chunyan Wu,Chunxia Su,Shengxiang Ren,Margarete Odenthal,Reinhard Buettner,Nan Fang,Caicun Zhou +24 more
TLDR
In this paper, the authors analyzed 42 tissue biopsy samples from stage III/IV NSCLC patients by single cell RNA sequencing and presented the large scale, single cell resolution profiles of advanced NSCLCs.Abstract:
Lung cancer is a highly heterogeneous disease. Cancer cells and cells within the tumor microenvironment together determine disease progression, as well as response to or escape from treatment. To map the cell type-specific transcriptome landscape of cancer cells and their tumor microenvironment in advanced non-small cell lung cancer (NSCLC), we analyze 42 tissue biopsy samples from stage III/IV NSCLC patients by single cell RNA sequencing and present the large scale, single cell resolution profiles of advanced NSCLCs. In addition to cell types described in previous single cell studies of early stage lung cancer, we are able to identify rare cell types in tumors such as follicular dendritic cells and T helper 17 cells. Tumors from different patients display large heterogeneity in cellular composition, chromosomal structure, developmental trajectory, intercellular signaling network and phenotype dominance. Our study also reveals a correlation of tumor heterogeneity with tumor associated neutrophils, which might help to shed light on their function in NSCLC. Comprehensive profiles of tumour and microenvironment are critical to understand heterogeneity in non-small cell lung cancer (NSCLC). Here, the authors profile 42 late-stage NSCLC patients with single-cell RNA-seq, revealing immune landscapes that are associated with cancer subtype or heterogeneity.read more
Citations
More filters
Journal ArticleDOI
Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities
TL;DR: Why defining AIR mechanisms at the tumour site should be a key focus to direct future drug development as well as practical approaches to improve current cancer therapy are discussed.
Journal ArticleDOI
Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities
Journal ArticleDOI
Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer
Jorge Luis Galeano Niño,Hanrui Wu,Kaitlyn D. LaCourse,Andrew G Kempchinsky,Alex A Baryiames,Brittany Barber,Neal D. Futran,Jeffrey J. Houlton,Cassandra L. Sather,Ewa Sicinska,A. Taylor,Samuel S. Minot,Christopher D Johnston,Susan Bullman +13 more
TL;DR: This article used GeoMx spatial profiling and single-cell RNA sequencing to identify cell-associated bacteria and the host cells with which they interact, as well as uncovering alterations in transcriptional pathways that are involved in inflammation, metastasis, cell dormancy and DNA repair.
Journal ArticleDOI
An Epigenetic Role of Mitochondria in Cancer
TL;DR: The roles of mitochondria in key metabolites required for epigenetics modification and in cell fate regulation are summarized and the current strategy in cancer therapies via targeting epigenetic modifiers and related enzymes in metabolic regulation is discussed.
Journal ArticleDOI
High-resolution single-cell atlas reveals diversity and plasticity of tissue-resident neutrophils in non-small cell lung cancer
Stefan Salcher,Gregor Sturm,Lena Horvath,Gerold Untergasser,Georgios Fotakis,Elisa Panizzolo,Agnieszka Martowicz,Georg Pall,Gabriele Gamerith,Martina M. Sykora,Florian Augustin,Katja Schmitz,Francesca Finotello,Dietmar Rieder,Sieghart Sopper,Dominik Wolf,Andreas Pircher,Zlatko Trajanoski +17 more
TL;DR: In this paper , the authors dissected the non-small cell lung cancer (NSCLC) tumor microenvironment at high resolution by integrating 1.283,972 single cells from 556 samples and 318 patients across 29 datasets, including cells with low mRNA content.
References
More filters
Journal ArticleDOI
Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks
Paul Shannon,Andrew Markiel,Owen Ozier,Nitin S. Baliga,Jonathan T. Wang,Daniel Ramage,Nada Amin,Benno Schwikowski,Trey Ideker +8 more
TL;DR: Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
Journal ArticleDOI
GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses.
TL;DR: GEPIA (Gene Expression Profiling Interactive Analysis) fills in the gap between cancer genomics big data and the delivery of integrated information to end users, thus helping unleash the value of the current data resources.
Journal ArticleDOI
The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells
Cole Trapnell,Davide Cacchiarelli,Davide Cacchiarelli,Jonna Grimsby,Prapti Pokharel,Shuqiang Li,Michael A. Morse,Michael A. Morse,Niall J. Lennon,Kenneth J. Livak,Tarjei S. Mikkelsen,Tarjei S. Mikkelsen,John L. Rinn,John L. Rinn,John L. Rinn +14 more
TL;DR: Monocle is described, an unsupervised algorithm that increases the temporal resolution of transcriptome dynamics using single-cell RNA-Seq data collected at multiple time points that revealed switch-like changes in expression of key regulatory factors, sequential waves of gene regulation, and expression of regulators that were not known to act in differentiation.
Journal ArticleDOI
Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer
Leena Gandhi,Delvys Rodriguez-Abreu,Shirish M. Gadgeel,Emilio Esteban,Enriqueta Felip,Flávia De Angelis,Manuel Domine,Philip Clingan,Maximilian J. Hochmair,Steven Francis Powell,Susanna Y.-S. Cheng,Helge Bischoff,Nir Peled,Francesco Grossi,Ross Jennens,Martin Reck,Rina Hui,Edward B. Garon,Michael Boyer,Belén Rubio-Viqueira,Silvia Novello,Takayasu Kurata,Jhanelle E. Gray,John Vida,Ziwen Wei,J. Yang,Harry Raftopoulos,M. Catherine Pietanza,Marina Chiara Garassino +28 more
TL;DR: In patients with previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum‐based drug resulted in significantly longer overall survival and progression‐free survival than chemotherapy alone.
Journal ArticleDOI
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Itay Tirosh,Benjamin Izar,Benjamin Izar,Sanjay M. Prakadan,Marc H. Wadsworth,Daniel J. Treacy,John J. Trombetta,Asaf Rotem,Asaf Rotem,Christopher Rodman,Christine G. Lian,George F. Murphy,Mohammad Fallahi-Sichani,Ken Dutton-Regester,Ken Dutton-Regester,Ken Dutton-Regester,Jia-Ren Lin,Ofir Cohen,Parin Shah,Diana Lu,Alex S. Genshaft,Travis K. Hughes,Carly G. K. Ziegler,Samuel W. Kazer,Aleth Gaillard,Kellie E. Kolb,Alexandra-Chloé Villani,Cory M. Johannessen,Aleksandr Andreev,Eliezer M. Van Allen,Eliezer M. Van Allen,Monica M. Bertagnolli,Monica M. Bertagnolli,Peter K. Sorger,Ryan J. Sullivan,Keith T. Flaherty,Dennie T. Frederick,Judit Jané-Valbuena,Charles H. Yoon,Charles H. Yoon,Orit Rozenblatt-Rosen,Alex K. Shalek,Aviv Regev,Aviv Regev,Aviv Regev,Levi A. Garraway +45 more
TL;DR: The cellular ecosystem of tumors is begin to unravel and how single-cell genomics offers insights with implications for both targeted and immune therapies is unraveled.
Related Papers (5)
Comprehensive T cell repertoire characterization of non-small cell lung cancer
Alexandre Reuben,Jiexin Zhang,Shin Heng Chiou,Rachel M. Gittelman,Jun Li,Won-Chul Lee,Junya Fujimoto,Carmen Behrens,Xiaoke Liu,Feng Wang,Kelly Quek,Chunlin Wang,Farrah Kheradmand,Runzhe Chen,Chi Wan Chow,Heather Lin,Chantale Bernatchez,Ali Jalali,Xin Hu,Chang-Jiun Wu,Agda Karina Eterovic,Edwin R. Parra,Erik Yusko,Ryan O. Emerson,Sharon Benzeno,Marissa Vignali,Xifeng Wu,Yuanqing Ye,Latasha Little,Curtis Gumbs,Xizeng Mao,Xingzhi Song,Samantha Tippen,Rebecca Thornton,Tina Cascone,Alexandra Snyder,Jennifer A. Wargo,Roy S. Herbst,Stephen G. Swisher,Humam Kadara,Cesar A. Moran,Neda Kalhor,Jianhua Zhang,Paul Scheet,Ara A. Vaporciyan,Boris Sepesi,Don L. Gibbons,Harlan Robins,Patrick Hwu,John V. Heymach,Padmanee Sharma,James P. Allison,Veera Baladandayuthapani,Jack Lee,Mark M. Davis,Ignacio I. Wistuba,P. Andrew Futreal,Jianjun Zhang +57 more
Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma.
Philip Bischoff,Philip Bischoff,Alexandra Trinks,Alexandra Trinks,Benedikt Obermayer,Jan Patrick Pett,Jennifer Wiederspahn,Florian Uhlitz,Florian Uhlitz,Xizi Liang,Annika Lehmann,Philipp Jurmeister,Philipp Jurmeister,Philipp Jurmeister,Aron Elsner,Tomasz Dziodzio,Tomasz Dziodzio,Jens-Carsten Rückert,Jens Neudecker,Christine S. Falk,Dieter Beule,Christine Sers,Christine Sers,Christine Sers,Markus Morkel,Markus Morkel,Markus Morkel,David Horst,David Horst,David Horst,Nils Blüthgen,Frederick Klauschen,Frederick Klauschen +32 more