Volume 567 Issue 7749, 28 March 2019

Cancer evolution

In this week’s issue, Rachel Rosenthal, Nicholas McGranahan, Charles Swanton and the TRACERx consortium explore the relationship between tumour evolution and the body’s immune system. Using RNA sequencing and estimates of the number of immune cells in tumours in 88 early-stage non-small-cell lung cancers, the researchers reveal how pressure from the immune microenvironment leads to selection for tumours that can readily evade the body’s defences. The results indicate that the immune microenvironment is highly variable between patients and even between different regions of the same tumour. The team suggests that tumour evolution is shaped by immunoediting that results in multiple distinct evolutionary routes to evade the immune response and that are associated with poorer clinical outcomes for patients after surgery. The cover shows a lung cancer with a diverse distribution of infiltrating immune CD8 T cells in the tumour microenvironment.

Cover image: Jeroen Claus/Phospho Biomedical Animation

This Week

News in Focus

Comment

Technology

    Technology Feature

  • Technology Feature |

    In the age of immunotherapy, cancer biologists are relying on a new generation of tools to learn how the interplay between tumours and immune cells shapes the course of disease.

    • Michael Eisenstein

    Collection:

Careers

Futures

  • Futures |

    Methods of preservation.

    • Robert Dawson

Research

    News & Views

  • News & Views |

    The function of histone proteins can be modified through addition or removal of certain chemical groups. The addition of a serotonin molecule is a newly found histone modification that could influence gene expression.

    • Marlene Cervantes
    •  & Paolo Sassone-Corsi
  • News & Views |

    The factors that contributed to the explosive nature of the 2015 Zika outbreak in the Americas are not well understood. A new analysis explores the link between prior dengue virus exposure and Zika virus infection.

    • Stephen S. Whitehead
    •  & Theodore C. Pierson
  • News & Views |

    Three studies have demonstrated the cooling and trapping of single strontium and ytterbium atoms in two-dimensional arrays. Such arrays could lead to advances in atomic-clock technology and in quantum simulation and computing.

    • Mark Saffman
  • News & Views |

    How Nature reported improved decision-making rules for betting in 1969, and an experiment in international wireless telephony from 1919.

  • News & Views |

    Materials called plastic crystals have been found to undergo huge temperature changes when subjected to small pressures near room temperature. Such materials could form the basis of future refrigeration technologies.

    • Claudio Cazorla
  • News & Views |

    A protein complex that moves molecules called lipopolysaccharides between the two cell-wall membranes of certain bacteria is a target for antibiotics. Structures now reveal how this complex delivers its load irreversibly.

    • Russell E. Bishop
  • Analysis

  • Analysis |

    The characterization of missense histone mutations that occur across several cancer types provides insight into the potential role of these mutations in altering chromatin structure and potentially contributing to tumour development.

    • Benjamin A. Nacev
    • , Lijuan Feng
    • , John D. Bagert
    • , Agata E. Lemiesz
    • , JianJiong Gao
    • , Alexey A. Soshnev
    • , Ritika Kundra
    • , Nikolaus Schultz
    • , Tom W. Muir
    •  & C. David Allis
  • Articles

  • Article |

    RNA sequencing data and tumour pathology observations of non-small-cell lung cancers indicate that the immune cell microenvironment exerts strong evolutionary selection pressures that shape the immune-evasion capacity of tumours.

    • Rachel Rosenthal
    • , Elizabeth Larose Cadieux
    • , Roberto Salgado
    • , Maise Al Bakir
    • , David A. Moore
    • , Crispin T. Hiley
    • , Tom Lund
    • , Miljana Tanić
    • , James L. Reading
    • , Kroopa Joshi
    • , Jake Y. Henry
    • , Ehsan Ghorani
    • , Gareth A. Wilson
    • , Nicolai J. Birkbak
    • , Mariam Jamal-Hanjani
    • , Selvaraju Veeriah
    • , Zoltan Szallasi
    • , Sherene Loi
    • , Matthew D. Hellmann
    • , Andrew Feber
    • , Benny Chain
    • , Javier Herrero
    • , Sergio A. Quezada
    • , Jonas Demeulemeester
    • , Peter Van Loo
    • , Stephan Beck
    • , Nicholas McGranahan
    • , Charles Swanton
    • , Charles Swanton
    • , Mariam Jamal-Hanjani
    • , Selvaraju Veeriah
    • , Justyna Czyzewska-Khan
    • , Diana Johnson
    • , Joanne Laycock
    • , Rachel Rosenthal
    • , Pat Gorman
    • , Robert E. Hynds
    • , Gareth Wilson
    • , Nicolai J. Birkbak
    • , Thomas B. K. Watkins
    • , Nicholas McGranahan
    • , Mickael Escudero
    • , Aengus Stewart
    • , Peter Van Loo
    • , Andrew Rowan
    • , Crispin Hiley
    • , Christopher Abbosh
    • , Jacki Goldman
    • , Richard Kevin Stone
    • , Tamara Denner
    • , Sophia Ward
    • , Emma Nye
    • , Kroopa Joshi
    • , Assma Ben Aissa
    • , Yien Ning Sophia Wong
    • , Andy Georgiou
    • , Sergio Quezada
    • , John A. Hartley
    • , Helen L. Lowe
    • , Javier Herrero
    • , David Lawrence
    • , Martin Hayward
    • , Nikolaos Panagiotopoulos
    • , Mary Falzon
    • , Elaine Borg
    • , Teresa Marafioti
    • , Sam M. Janes
    • , Martin Forster
    • , Tanya Ahmad
    • , Siow Ming Lee
    • , Dionysis Papadatos-Pastos
    • , Dawn Carnell
    • , Ruheena Mendes
    • , Jeremy George
    • , Asia Ahmed
    • , Magali Taylor
    • , Junaid Choudhary
    • , Yvonne Summers
    • , Raffaele Califano
    • , Paul Taylor
    • , Rajesh Shah
    • , Piotr Krysiak
    • , Kendadai Rammohan
    • , Eustace Fontaine
    • , Richard Booton
    • , Matthew Evison
    • , Phil Crosbie
    • , Stuart Moss
    • , Leena Joseph
    • , Paul Bishop
    • , Anne Marie Quinn
    • , Helen Doran
    • , Angela Leek
    • , Phil Harrison
    • , Katrina Moore
    • , Rachael Waddington
    • , Juliette Novasio
    • , Fiona Blackhall
    • , Jane Rogan
    • , Elaine Smith
    • , Caroline Dive
    • , Jonathan Tugwood
    • , Ged Brady
    • , Dominic G. Rothwell
    • , Jackie Pierce
    • , Sakshi Gulati
    • , Babu Naidu
    • , Gerald Langman
    • , Simon Trotter
    • , Hollie Bancroft
    • , Amy Kerr
    • , Salma Kadiri
    • , Gary Middleton
    • , Madava Djearaman
    • , Dean Fennell
    • , Jacqui A. Shaw
    • , John Le Quesne
    • , David A. Moore
    • , Apostolos Nakas
    • , Sridhar Rathinam
    • , William Monteiro
    • , Hilary Marshall
    • , Louise Nelson
    • , Joan Riley
    • , Lindsay Primrose
    • , Luke Martinson
    • , Girija Anand
    • , Sajid Khan
    • , Marianne Nicolson
    • , Keith Kerr
    • , Shirley Palmer
    • , Hardy Remmen
    • , Joy Miller
    • , Keith Buchan
    • , Mahendran Chetty
    • , Lesley Gomersall
    • , Jason Lester
    • , Fiona Morgan
    • , Haydn Adams
    • , Helen Davies
    • , Malgorzata Kornaszewska
    • , Richard Attanoos
    • , Sara Lock
    • , Mairead MacKenzie
    • , Maggie Wilcox
    • , Harriet Bell
    • , Allan Hackshaw
    • , Yenting Ngai
    • , Sean Smith
    • , Nicole Gower
    • , Christian Ottensmeier
    • , Serena Chee
    • , Benjamin Johnson
    • , Aiman Alzetani
    • , Emily Shaw
    • , Eric Lim
    • , Paulo De Sousa
    • , Monica Tavares Barbosa
    • , Alex Bowman
    • , Simon Jordan
    • , Alexandra Rice
    • , Hilgardt Raubenheimer
    • , Harshil Bhayani
    • , Morag Hamilton
    • , Natalie Mensah
    • , Lyn Ambrose
    • , Anand Devaraj
    • , Hema Chavan
    • , Andrew G. Nicholson
    • , Kelvin Lau
    • , Michael Sheaff
    • , Peter Schmid
    • , John Conibear
    • , Veni Ezhil
    • , Vineet Prakash
    • , Peter Russell
    • , Teresa Light
    • , Tracey Horey
    • , Sarah Danson
    • , Jonathan Bury
    • , John Edwards
    • , Jennifer Hill
    • , Sue Matthews
    • , Yota Kitsanta
    • , Kim Suvarna
    • , Patricia Fisher
    • , Michael Shackcloth
    • , John Gosney
    • , Sarah Feeney
    • , Julius Asante-Siaw
    • , Kim Ryanna
    • , Alan Dawson
    • , Mohamad Tuffail
    • , Amrita Bajaj
    • , Jan Brozik
    • , Harriet Walter
    • , Nicolas Carey
    • , Gillian Price
    • , Kayleigh Gilbert
    • , Joanne Webb
    • , Akshay Patel
    • , Anshuman Chaturvedi
    • , Felice Granato
    • , Katie Baker
    • , Mathew Carter
    • , Lynsey Priest
    • , Matthew G. Krebs
    • , Colin Lindsay
    • , Fabio Gomes
    • , Francesca Chemie
    • , Robert George
    • , Davide Patrini
    • , Reena Khiroya
    • , Penny Shaw
    • , Marcin Skrzypski
    • , Mariana Werner Sunderland
    • , James L. Reading
    • , Carmella Beastall
    • , Nagina Mangal
    • , Karl Peggs
    • , Emilia Lim
    • , Maise Al-Bakir
    • , Neal Navani
    • , Marco Scarci
    • , Leah Ensell
    • , Dhruva Biswas
    • , Roberto Salgado
    • , Maryam Razaq
    • , Jerome Nicod
    • , Stephan Beck
    • , Saioa Lopez
    • , Ariana Huebner
    • , Michelle Dietzen
    • , Thanos Mourikis
    • , Toyin Adefila-Ideozu
    • , Sofina Begum
    • , Henriette Klein
    • , Aleksander Mani
    • , Soraia Carvalho
    • , Daniel Kaniu
    • , Cristina Realingo
    • , Mpho Malima
    • , Sarah Booth
    • , Louise Lim
    • , Jagan Rao
    • , Sara Tenconi
    • , Laura Socci
    • , Faith Kibutu
    • , Michael Agyemang
    • , Robin Young
    • , Kevin G. Blyth
    • , Craig Dick
    • , Alan Kirk
    •  & Andrew Kidd
  • Article |

    Cryo-electron microscopy structures of LptB2FGC, in nucleotide-free and vanadate-trapped states, reveal the mechanism of lipopolysaccharide extraction from the inner membrane of Gram-negative bacteria and a role for LptC in efficient lipopolysaccharide transport.

    • Yanyan Li
    • , Benjamin J. Orlando
    •  & Maofu Liao
  • Letters

  • Letter |

    The accuracy of computations on noisy, near-term quantum systems can be enhanced by extrapolating results from experiments with various noise levels, without requiring additional hardware modifications.

    • Abhinav Kandala
    • , Kristan Temme
    • , Antonio D. Córcoles
    • , Antonio Mezzacapo
    • , Jerry M. Chow
    •  & Jay M. Gambetta
  • Letter |

    Angle-resolved photoemission spectroscopy measurements in CoSi reveal the presence of unconventional chiral fermions near the Fermi level, with giant surface Fermi arcs and one pair of well separated chiral nodes.

    • Zhicheng Rao
    • , Hang Li
    • , Tiantian Zhang
    • , Shangjie Tian
    • , Chenghe Li
    • , Binbin Fu
    • , Cenyao Tang
    • , Le Wang
    • , Zhilin Li
    • , Wenhui Fan
    • , Jiajun Li
    • , Yaobo Huang
    • , Zhehong Liu
    • , Youwen Long
    • , Chen Fang
    • , Hongming Weng
    • , Youguo Shi
    • , Hechang Lei
    • , Yujie Sun
    • , Tian Qian
    •  & Hong Ding
  • Letter |

    Angle-resolved photoemission spectroscopy measurements reveal that CoSi and RhSi are nearly ideal topological conductors, with structural chirality and surface helicoid arcs of topological charge ±2 arising from bulk multifold chiral states.

    • Daniel S. Sanchez
    • , Ilya Belopolski
    • , Tyler A. Cochran
    • , Xitong Xu
    • , Jia-Xin Yin
    • , Guoqing Chang
    • , Weiwei Xie
    • , Kaustuv Manna
    • , Vicky Süß
    • , Cheng-Yi Huang
    • , Nasser Alidoust
    • , Daniel Multer
    • , Songtian S. Zhang
    • , Nana Shumiya
    • , Xirui Wang
    • , Guang-Qiang Wang
    • , Tay-Rong Chang
    • , Claudia Felser
    • , Su-Yang Xu
    • , Shuang Jia
    • , Hsin Lin
    •  & M. Zahid Hasan
  • Letter |

    Colossal barocaloric effects are observed in the plastic crystal neopentylglycol and found to originate from the extensive molecular orientational disorder, giant compressibility and highly anharmonic lattice dynamics of the material.

    • Bing Li
    • , Yukinobu Kawakita
    • , Seiko Ohira-Kawamura
    • , Takeshi Sugahara
    • , Hui Wang
    • , Jingfan Wang
    • , Yanna Chen
    • , Saori I. Kawaguchi
    • , Shogo Kawaguchi
    • , Koji Ohara
    • , Kuo Li
    • , Dehong Yu
    • , Richard Mole
    • , Takanori Hattori
    • , Tatsuya Kikuchi
    • , Shin-ichiro Yano
    • , Zhao Zhang
    • , Zhe Zhang
    • , Weijun Ren
    • , Shangchao Lin
    • , Osami Sakata
    • , Kenji Nakajima
    •  & Zhidong Zhang
  • Letter |

    A double-layered halide architecture for perovskite solar cells enables the use of dopant-free poly(3-hexylthiophene) as a hole-transport material, forming stable and scalable devices with a certified power conversion efficiency of 22.7 per cent.

    • Eui Hyuk Jung
    • , Nam Joong Jeon
    • , Eun Young Park
    • , Chan Su Moon
    • , Tae Joo Shin
    • , Tae-Youl Yang
    • , Jun Hong Noh
    •  & Jangwon Seo
  • Letter |

    Estimates of spatial patterns of nitrogen discharge into water bodies across China between 1955 and 2014 show that current discharge rates are almost three times the acceptable threshold, and ways to restore a clean water environment are suggested.

    • ChaoQing Yu
    • , Xiao Huang
    • , Han Chen
    • , H. Charles J. Godfray
    • , Jonathon S. Wright
    • , Jim W. Hall
    • , Peng Gong
    • , ShaoQiang Ni
    • , ShengChao Qiao
    • , GuoRui Huang
    • , YuChen Xiao
    • , Jie Zhang
    • , Zhao Feng
    • , XiaoTang Ju
    • , Philippe Ciais
    • , Nils Chr. Stenseth
    • , Dag O. Hessen
    • , ZhanLi Sun
    • , Le Yu
    • , WenJia Cai
    • , HaoHuan Fu
    • , XiaoMeng Huang
    • , Chi Zhang
    • , HongBin Liu
    •  & James Taylor
  • Letter |

    A proof-of-concept clinical trial of patients with histiocytoses with MAPK-pathway mutations showed durable responses to treatment with the MEK1 and MEK2 inhibitor cobimetinib, which indicates that histiocytic neoplasms are dependent on MAPK signalling.

    • Eli L. Diamond
    • , Benjamin H. Durham
    • , Gary A. Ulaner
    • , Esther Drill
    • , Justin Buthorn
    • , Michelle Ki
    • , Lillian Bitner
    • , Hana Cho
    • , Robert J. Young
    • , Jasmine H. Francis
    • , Raajit Rampal
    • , Mario Lacouture
    • , Lynn A. Brody
    • , Neval Ozkaya
    • , Ahmet Dogan
    • , Neal Rosen
    • , Alexia Iasonos
    • , Omar Abdel-Wahab
    •  & David M. Hyman
  • Letter |

    Tolerant T cells display characteristic patterns of gene expression and epigenetics that are distinct from other types of T cells and are orchestrated by the transcription factor NR4A1.

    • Xindong Liu
    • , Yun Wang
    • , Huiping Lu
    • , Jing Li
    • , Xiaowei Yan
    • , Minglu Xiao
    • , Jing Hao
    • , Andrei Alekseev
    • , Hiep Khong
    • , Tenghui Chen
    • , Rui Huang
    • , Jin Wu
    • , Qiwen Zhao
    • , Qi Wu
    • , Senlin Xu
    • , Xiaohu Wang
    • , Wei Jin
    • , Shicang Yu
    • , Yan Wang
    • , Lai Wei
    • , Aibo Wang
    • , Bo Zhong
    • , Ling Ni
    • , Xiaolong Liu
    • , Roza Nurieva
    • , Lilin Ye
    • , Qiang Tian
    • , Xiu-Wu Bian
    •  & Chen Dong
  • Letter |

    Transfer of NR4A-deficient T cells expressing chimeric antigen receptors is shown to reduce tumour burden and increase survival by shifting T cell transcriptional programs away from exhaustion and towards increased effector function.

    • Joyce Chen
    • , Isaac F. López-Moyado
    • , Hyungseok Seo
    • , Chan-Wang J. Lio
    • , Laura J. Hempleman
    • , Takashi Sekiya
    • , Akihiko Yoshimura
    • , James P. Scott-Browne
    •  & Anjana Rao
  • Letter |

    In serotonin-rich tissues, tissue transglutaminase 2 is able to attach serotonin to a glutamine residue in histone H3; this modification mediates permissive gene expression in these tissues.

    • Lorna A. Farrelly
    • , Robert E. Thompson
    • , Shuai Zhao
    • , Ashley E. Lepack
    • , Yang Lyu
    • , Natarajan V. Bhanu
    • , Baichao Zhang
    • , Yong-Hwee E. Loh
    • , Aarthi Ramakrishnan
    • , Krishna C. Vadodaria
    • , Kelly J. Heard
    • , Galina Erikson
    • , Tomoyoshi Nakadai
    • , Ryan M. Bastle
    • , Bradley J. Lukasak
    • , Henry Zebroski III
    • , Natalia Alenina
    • , Michael Bader
    • , Olivier Berton
    • , Robert G. Roeder
    • , Henrik Molina
    • , Fred H. Gage
    • , Li Shen
    • , Benjamin A. Garcia
    • , Haitao Li
    • , Tom W. Muir
    •  & Ian Maze
  • Letter |

    In patient-derived xenograft models of breast cancer in mice, an increase in stress hormones during progression or treatment with their synthetic derivatives activates the glucocorticoid receptor, and results in increased metastatic colonization and reduced survival.

    • Milan M. S. Obradović
    • , Baptiste Hamelin
    • , Nenad Manevski
    • , Joana Pinto Couto
    • , Atul Sethi
    • , Marie-May Coissieux
    • , Simone Münst
    • , Ryoko Okamoto
    • , Hubertus Kohler
    • , Alexander Schmidt
    •  & Mohamed Bentires-Alj
  • Letter |

    In human neuroblastoma tumours, MYCN is engaged in a USP11–BRCA1-dependent manner to suppress the accumulation of stalled RNAPII and induces both the activation and repression of genes.

    • Steffi Herold
    • , Jacqueline Kalb
    • , Gabriele Büchel
    • , Carsten P. Ade
    • , Apoorva Baluapuri
    • , Jiajia Xu
    • , Jan Koster
    • , Daniel Solvie
    • , Anne Carstensen
    • , Christina Klotz
    • , Sabrina Rodewald
    • , Christina Schülein-Völk
    • , Matthias Dobbelstein
    • , Elmar Wolf
    • , Jan Molenaar
    • , Rogier Versteeg
    • , Susanne Walz
    •  & Martin Eilers
  • Letter |

    Crystal structures of a five-protein complex comprising the inner-membrane components of the bacterial lipopolysaccharide transporter provide insight into the mechanism of extraction of lipopolysaccharide from the inner membrane and its transport to the outer membrane.

    • Tristan W. Owens
    • , Rebecca J. Taylor
    • , Karanbir S. Pahil
    • , Blake R. Bertani
    • , Natividad Ruiz
    • , Andrew C. Kruse
    •  & Daniel Kahne

Amendments & Corrections

  • Publisher Correction |

    • Dmitri Lodygin
    • , Moritz Hermann
    • , Nils Schweingruber
    • , Cassandra Flügel-Koch
    • , Takashi Watanabe
    • , Corinna Schlosser
    • , Arianna Merlini
    • , Henrike Körner
    • , Hsin-Fang Chang
    • , Henrike J. Fischer
    • , Holger M. Reichardt
    • , Marta Zagrebelsky
    • , Brit Mollenhauer
    • , Sebastian Kügler
    • , Dirk Fitzner
    • , Jens Frahm
    • , Christine Stadelmann
    • , Michael Haberl
    • , Francesca Odoardi
    •  & Alexander Flügel

Collections

  • Focal Point |

    AI and big data healthcare in Korea

    A large investor in R&D, South Korea’s culture of early technology adoption, combined with its strong computing infrastructure and biological research strengths, make the country an obvious personalized medicine testbed.

  • Spotlight |

    Cancer

    From examining the longevity of naked mole rats to manipulating microbubbles with drugs and magnets, to keeping mice up past their bedtimes. Here’s how researchers are finding new ways to treat cancer.

  • Career Guide |

    Career Guide: Germany

    Germany is a world leader in scientific research and a top destination for individual researchers. Learn how the country is coupling its scientific work with ambitious manufacturing goals, how it’s becoming more diverse in a globalized research system, and how it’s becoming a powerhouse of renewable energy. See where you can fit in.

Newsletter Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing