Open Access
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Itay Tirosh,Benjamin Izar,Daniel J. Treacy,John J. Trombetta,Asaf Rotem,Christopher Rodman,Christine G. Lian,George F. Murphy,Mohammad Fallahi-Sichani,Ken Dutton-Regester,Jia-Ren Lin,Ofir Cohen,Parin Shah,Diana Lu,Alexandra-Chloé Villani,Aleksandr Andreev,E.M. Van Allen,Monica M. Bertagnolli,Peter K. Sorger,Ryan J. Sullivan,Keith T. Flaherty,Dennie T. Frederick,Judit Jané-Valbuena,Orit Rozenblatt-Rosen,Sanjay M. Prakadan,Marc H. Wadsworth,Alex S. Genshaft,Travis K. Hughes,Carly G. K. Ziegler,Samuel W. Kazer,Alethe Gaillard de Saint Germain,Kellie E. Kolb,Cory M. Johannessen,Clifford H. Yoon,Alex K. Shalek,Aviv Regev,Levi A. Garraway +36 more
Reads0
Chats0
TLDR
Tirosh et al. as discussed by the authors applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells.Abstract:
Single-cell expression profiles of melanoma Tumors harbor multiple cell types that are thought to play a role in the development of resistance to drug treatments. Tirosh et al. used single-cell sequencing to investigate the distribution of these differing genetic profiles within melanomas. Many cells harbored heterogeneous genetic programs that reflected two different states of genetic expression, one of which was linked to resistance development. Following drug treatment, the resistance-linked expression state was found at a much higher level. Furthermore, the environment of the melanoma cells affected their gene expression programs. Science, this issue p. 189 Melanoma cells show transcriptional heterogeneity. To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells. Malignant cells within the same tumor displayed transcriptional heterogeneity associated with the cell cycle, spatial context, and a drug-resistance program. In particular, all tumors harbored malignant cells from two distinct transcriptional cell states, such that tumors characterized by high levels of the MITF transcription factor also contained cells with low MITF and elevated levels of the AXL kinase. Single-cell analyses suggested distinct tumor microenvironmental patterns, including cell-to-cell interactions. Analysis of tumor-infiltrating T cells revealed exhaustion programs, their connection to T cell activation and clonal expansion, and their variability across patients. Overall, we begin to unravel the cellular ecosystem of tumors and how single-cell genomics offers insights with implications for both targeted and immune therapies.read more
Citations
More filters
Integrative analysis of 111 reference human epigenomes
Anshul Kundaje,Wouter Meuleman,Jason Ernst,Angela Yen,Pouya Kheradpour,Zhizhuo Zhang,Jianrong Wang,Lucas D. Ward,Abhishek Sarkar,Gerald Quon,Matthew L. Eaton,Yi-Chieh Wu,Andreas R. Pfenning,Xinchen Wang,Melina Claussnitzer,Yaping Liu,Mukul S. Bansal,Soheil Feizi-Khankandi,Ah Ram Kim,Richard C Sallari,Nicholas A Sinnott-Armstrong,Laurie A. Boyer,Elizabeta Gjoneska,Li-Huei Tsai,Manolis Kellis +24 more
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Revealing the vectors of cellular identity with single-cell genomics
TL;DR: Single-cell genomics has now made it possible to create a comprehensive atlas of human cells and has reopened definitions of a cell's identity and of the ways in which identity is regulated by the cell's molecular circuitry.
Journal ArticleDOI
The Tabula Sapiens: a multiple organ single cell transcriptomic atlas of humans
TL;DR: A human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor, enabled molecular characterization of more than 400 cell types, their distribution across tissues and tissue specific variation in gene expression.
Journal ArticleDOI
Decade-long leukaemia remissions with persistence of CD4+ CAR T cells
J. Joseph Melenhorst,Gregory M. Chen,Meng Wang,David L. Porter,Changya Chen,McKensie Collins,Peng Gao,Shovik Bandyopadhyay,Hongxing Sun,Ziran Zhao,Stefan Lundh,Iulian Pruteanu-Malinici,Christopher L. Nobles,Sayantan Maji,Noelle V. Frey,Saar Gill,Lifeng Tian,Irina Kulikovskaya,Minnal Gupta,David E Ambrose,Megan M. Davis,Joseph A. Fraietta,Jennifer Brogdon,Regina M. Young,Anne Chew,Bruce L. Levine,Don L. Siegel,Cécile Alanio,E. John Wherry,Frederic D. Bushman,Simon F. Lacey,Kai Tan,Carl H. June +32 more
TL;DR: In this article , the authors studied long-lasting CD19-redirected chimeric antigen receptor (CAR) T cells in two patients with chronic lymphocytic leukaemia who achieved a complete remission in 2010.
Journal ArticleDOI
Macrophages as tools and targets in cancer therapy
TL;DR: In this paper , the authors proposed a set of macrophage-targeting strategies that include inhibitors of cytokines and chemokines involved in the recruitment and polarization of tumour-promoting myeloid cells as well as activators of their antitumorigenic and immunostimulating functions.
References
More filters
Journal ArticleDOI
The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications.
Yuanyuan Zhang,Zemin Zhang +1 more
TL;DR: A review of the recent progress in cancer immunotherapy is outlined, particularly by focusing on landmark studies and the recent single-cell characterization of tumor-associated immune cells, and the phenotypic diversities of intratumoral immune cells and their connections with cancer Immunotherapy are summarized.
Journal ArticleDOI
Exhaustion of tumor-specific CD8(+) T cells in metastases from melanoma patients
Lukas Baitsch,Petra Baumgaertner,Estelle Devevre,Sunil K. Raghav,Amandine Legat,Leticia Barba,Sébastien Wieckowski,Hanifa Bouzourene,Bart Deplancke,Pedro Romero,Nathalie Rufer,Daniel E. Speiser +11 more
TL;DR: The identified exhaustion profile revealed extended molecular alterations in Melan-A/MART-1-specific T cells isolated from metastases from patients with melanoma expressed a large variety of genes associated with T cell exhaustion.
Journal ArticleDOI
Landscape and Dynamics of Single Immune Cells in Hepatocellular Carcinoma.
Qiming Zhang,Yao He,Nan Luo,Shashank J. Patel,Yanjie Han,Ranran Gao,Madhura Modak,Sebastian Carotta,Christian Haslinger,David Kind,Gregory W. Peet,Guojie Zhong,Shuangjia Lu,Weihua Zhu,Yilei Mao,Mengmeng Xiao,Michael Bergmann,Xueda Hu,Sid P. Kerkar,Anne Vogt,Stefan Pflanz,Kang Liu,Jirun Peng,Jirun Peng,Xianwen Ren,Zemin Zhang +25 more
TL;DR: The dynamic properties of diverse CD45+ cell types revealed by this study add new dimensions to the immune landscape of HCC.
Journal ArticleDOI
Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer
Woosung Chung,Hye Hyeon Eum,Hye Hyeon Eum,Hae Ock Lee,Hae Ock Lee,Kyung Min Lee,Han-Byoel Lee,Kyu-Tae Kim,Han Suk Ryu,Sangmin Kim,Jeong Eon Lee,Yeon Hee Park,Zhengyan Kan,Wonshik Han,Woong-Yang Park,Woong-Yang Park +15 more
TL;DR: The results illustrate that the breast cancer transcriptome has a wide range of intratumoral heterogeneity, which is shaped by the tumour cells and immune cells in the surrounding microenvironment.
Journal ArticleDOI
Defining ‘T cell exhaustion’
Christian U. Blank,W. Nicholas Haining,Werner Held,Patrick G. Hogan,Patrick G. Hogan,Axel Kallies,Enrico Lugli,Rachel C. Lynn,Mary Philip,Anjana Rao,Anjana Rao,Nicholas P. Restifo,Andrea Schietinger,Ton N. Schumacher,Pamela L. Schwartzberg,Arlene H. Sharpe,Daniel E. Speiser,E. John Wherry,Benjamin Youngblood,Dietmar Zehn +19 more
TL;DR: In this Viewpoint article, 18 experts in the field tell us what exhaustion means to them, ranging from complete lack of effector function to altered functionality to prevent immunopathology, with potential differences between cancer and chronic infection.
Related Papers (5)
Abstract 4380: Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-sequencing
Benjamin Izar,Itay Tirsh,Sanjay Prakadan,Marc Wadsworth,Daniel J. Treacy,John J. Trombetta,Asaf Rotem,Christine G. Lian,George F. Murphy,Mohammad Fallahi-Sichani,Ken Dutton-Regester,Jia-Ren Lin,Judit Jané-Valbuena,Orit Rozenblatt-Rosen,Charles H. Yoon,Alex K. Shalek,Aviv Regev,Levi A. Garraway +17 more
Understanding tumor-infiltrating lymphocytes by single cell RNA sequencing.
Xianwen Ren,Zemin Zhang +1 more