Volume 25 Issue 10, October 2019

Volume 25 Issue 10

TRACERx Lung: intratumor heterogeneity and clinical outcomes

Lung cancer is the leading cause of cancer-related deaths worldwide, with a five-year relative survival rate of 4% in the metastatic setting. In this issue, three reports from the TRACERx (TRAcking Cancer Evolution through therapy (Rx)) lung study provide insights into tumor evolution and intratumor heterogeneity that may facilitate the development of biomarkers and improve therapeutic outcomes for patients.

See: Dive and colleagues, Swanton and colleagues and Chain and colleagues.

Image credit: Jeroen Claus. Cover design: Erin Dewalt

Editorial

  • Editorial |

    Nature Medicine is taking a comprehensive approach for reporting clinical studies with the aim to increase transparency, promote rigorous reporting standards and engage with the community to meet the challenges of contemporary medicine.

News Feature

Turning Points

  • Turning Points |

    Patrícia Brasil is head of the Laboratory of Acute Febrile Illness of the National Institute of Infectious Diseases Evandro Chagas, Fiocruz, and professor of tropical medicine and clinical research in the postgraduate programs of Fiocruz in Rio de Janeiro, Brazil.

    • Patrícia Brasil

Comment

  • Comment |

    As artificial intelligence moves into the realm of clinical trials, consideration is needed on whether the current CONSORT and SPIRIT reporting statements are sufficient to ensure transparency.

    • Xiaoxuan Liu
    • , Samantha Cruz Rivera
    • , Livia Faes
    • , Lavinia Ferrante di Ruffano
    • , Christopher Yau
    • , Pearse A. Keane
    • , Hutan Ashrafian
    • , Ara Darzi
    • , Sebastian J. Vollmer
    • , Jonathan Deeks
    • , Lucas Bachmann
    • , Christopher Holmes
    • , An Wen Chan
    • , David Moher
    • , Melanie J. Calvert
    •  & Alastair K. Denniston

Research Highlights

News & Views

  • News & Views |

    Antibodies elicited by the widely deployed rVSV-EBOV Ebola virus vaccine mirror those of disease survivors, animal models and other vaccine platforms. Notably, neutralizing antibodies are consistently elicited from a recurring pair of germline genes.

    • Erica Ollmann Saphire
  • News & Views |

    A novel oral capsule can deploy microneedle patches that release drugs into the intestinal wall for uptake into the bloodstream as shown in animal studies, thereby avoiding injections.

    • Mark R. Prausnitz
    • , Yasmine Gomaa
    •  & Wei Li
  • News & Views |

    An engineered truncated gene derived from the dystrophin-related protein (utrophin), prevents pathology without an immune response in an animal model of Duchenne muscular dystrophy (DMD) gene therapy.

    • Kay E. Davies
    •  & Jeffrey S. Chamberlain
  • News & Views |

    Single-cell RNA sequencing characterizes clonal dynamics and distinct cellular states contributing to intratumoral heterogeneity in glioblastoma and medulloblastoma.

    • Maleeha A. Qazi
    • , David Bakhshinyan
    •  & Sheila K. Singh

Perspectives

  • Perspective |

    Rare genetic diseases frequently involve a neuropsychiatric component for which a defined framework of investigation will expedite our understanding for these diseases as a whole.

    • Stephan J. Sanders
    • , Mustafa Sahin
    • , Joseph Hostyk
    • , Audrey Thurm
    • , Sebastien Jacquemont
    • , Paul Avillach
    • , Elise Douard
    • , Christa L. Martin
    • , Meera E. Modi
    • , Andres Moreno-De-Luca
    • , Armin Raznahan
    • , Alan Anticevic
    • , Ricardo Dolmetsch
    • , Guoping Feng
    • , Daniel H. Geschwind
    • , David C. Glahn
    • , David B. Goldstein
    • , David H. Ledbetter
    • , Jennifer G. Mulle
    • , Sergiu P. Pasca
    • , Rodney Samaco
    • , Jonathan Sebat
    • , Anne Pariser
    • , Thomas Lehner
    • , Raquel E. Gur
    •  & Carrie E. Bearden

Review Articles

Brief Communications

  • Brief Communication |

    This first-in-human study assessed the feasibility of vaginal microbiome transplantation from healthy donors as a therapeutic alternative for patients suffering from symptomatic, intractable and recurrent bacterial vaginosis.

    • Ahinoam Lev-Sagie
    • , Debra Goldman-Wohl
    • , Yotam Cohen
    • , Mally Dori-Bachash
    • , Avner Leshem
    • , Uria Mor
    • , Jacob Strahilevitz
    • , Allon E. Moses
    • , Hagit Shapiro
    • , Simcha Yagel
    •  & Eran Elinav

Letters

  • Letter |

    A gene therapy vector expressing micro-utrophin provides functional replacement of lost dystrophin, and lacks the adverse immunogenicity associated with direct dystrophin therapy, in rodent and canine models of Duchenne muscular dystrophy.

    • Yafeng Song
    • , Leon Morales
    • , Alock S. Malik
    • , Andrew F. Mead
    • , Christopher D. Greer
    • , Marilyn A. Mitchell
    • , Mihail T. Petrov
    • , Leonard T. Su
    • , Margaret E. Choi
    • , Shira T. Rosenblum
    • , Xiangping Lu
    • , Daniel J. VanBelzen
    • , Ranjith K. Krishnankutty
    • , Frederick J. Balzer
    • , Emanuele Loro
    • , Robert French
    • , Kathleen J. Propert
    • , Shangzhen Zhou
    • , Benjamin W. Kozyak
    • , Peter P. Nghiem
    • , Tejvir S. Khurana
    • , Joe N. Kornegay
    •  & Hansell H. Stedman
  • Letter |

    A luminal unfolding microneedle injector device (LUMI) is engineered as a custom capsule capable of efficient biologic macromolecular drug delivery into the bloodstream via selective deployment within the gastrointestinal tract.

    • Alex Abramson
    • , Ester Caffarel-Salvador
    • , Vance Soares
    • , Daniel Minahan
    • , Ryan Yu Tian
    • , Xiaoya Lu
    • , David Dellal
    • , Yuan Gao
    • , Soyoung Kim
    • , Jacob Wainer
    • , Joy Collins
    • , Siddartha Tamang
    • , Alison Hayward
    • , Tadayuki Yoshitake
    • , Hsiang-Chieh Lee
    • , James Fujimoto
    • , Johannes Fels
    • , Morten Revsgaard Frederiksen
    • , Ulrik Rahbek
    • , Niclas Roxhed
    • , Robert Langer
    •  & Giovanni Traverso
  • Letter |

    Deep convolutional neural networks predict survival of mesothelioma patients and identify histological features associated with outcome that transcend current histological classifications.

    • Pierre Courtiol
    • , Charles Maussion
    • , Matahi Moarii
    • , Elodie Pronier
    • , Samuel Pilcer
    • , Meriem Sefta
    • , Pierre Manceron
    • , Sylvain Toldo
    • , Mikhail Zaslavskiy
    • , Nolwenn Le Stang
    • , Nicolas Girard
    • , Olivier Elemento
    • , Andrew G. Nicholson
    • , Jean-Yves Blay
    • , Françoise Galateau-Sallé
    • , Gilles Wainrib
    •  & Thomas Clozel
  • Letter |

    Whole-genome sequencing in triple-negative breast cancer supports the prognostic value of the HRDetect mutational-signature-based algorithm for improving patient stratification in a real-world, population-based clinical diagnostic setting.

    • Johan Staaf
    • , Dominik Glodzik
    • , Ana Bosch
    • , Johan Vallon-Christersson
    • , Christel Reuterswärd
    • , Jari Häkkinen
    • , Andrea Degasperi
    • , Tauanne Dias Amarante
    • , Lao H. Saal
    • , Cecilia Hegardt
    • , Hilary Stobart
    • , Anna Ehinger
    • , Christer Larsson
    • , Lisa Rydén
    • , Niklas Loman
    • , Martin Malmberg
    • , Anders Kvist
    • , Hans Ehrencrona
    • , Helen R. Davies
    • , Åke Borg
    •  & Serena Nik-Zainal
  • Letter |

    Pulmonary venous tumor cells disseminating before tumor resection are heterogeneous, predict relapse and seed future metastasis of lung cancer

    • Francesca Chemi
    • , Dominic G. Rothwell
    • , Nicholas McGranahan
    • , Sakshi Gulati
    • , Chris Abbosh
    • , Simon P. Pearce
    • , Cong Zhou
    • , Gareth A. Wilson
    • , Mariam Jamal-Hanjani
    • , Nicolai Birkbak
    • , Jackie Pierce
    • , Chang Sik Kim
    • , Saba Ferdous
    • , Deborah J. Burt
    • , Daniel Slane-Tan
    • , Fabio Gomes
    • , David Moore
    • , Rajesh Shah
    • , Maise Al Bakir
    • , Crispin Hiley
    • , Selvaraju Veeriah
    • , Yvonne Summers
    • , Philip Crosbie
    • , Sophia Ward
    • , Barbara Mesquita
    • , Marek Dynowski
    • , Dhruva Biswas
    • , Jonathan Tugwood
    • , Fiona Blackhall
    • , Crispin Miller
    • , Allan Hackshaw
    • , Ged Brady
    • , Charles Swanton
    •  & Caroline Dive
  • Letter |

    TRACERx Lung: Intratumoral transcriptional heterogeneity, which often hinders the development of clinically useful RNA-expression-biased biomarkers for cancer, can now be overcome with an approach for the identification of clonal expression biomarkers.

    • Dhruva Biswas
    • , Nicolai J. Birkbak
    • , Rachel Rosenthal
    • , Crispin T. Hiley
    • , Emilia L. Lim
    • , Krisztian Papp
    • , Stefan Boeing
    • , Marcin Krzystanek
    • , Dijana Djureinovic
    • , Linnea La Fleur
    • , Maria Greco
    • , Balázs Döme
    • , János Fillinger
    • , Hans Brunnström
    • , Yin Wu
    • , David A. Moore
    • , Marcin Skrzypski
    • , Christopher Abbosh
    • , Kevin Litchfield
    • , Maise Al Bakir
    • , Thomas B. K. Watkins
    • , Selvaraju Veeriah
    • , Gareth A. Wilson
    • , Mariam Jamal-Hanjani
    • , Judit Moldvay
    • , Johan Botling
    • , Arul M. Chinnaiyan
    • , Patrick Micke
    • , Allan Hackshaw
    • , Jiri Bartek
    • , Istvan Csabai
    • , Zoltan Szallasi
    • , Javier Herrero
    • , Nicholas McGranahan
    •  & Charles Swanton

Articles

  • Article |

    A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

    • Kroopa Joshi
    • , Marc Robert de Massy
    • , Mazlina Ismail
    • , James L. Reading
    • , Imran Uddin
    • , Annemarie Woolston
    • , Emine Hatipoglu
    • , Theres Oakes
    • , Rachel Rosenthal
    • , Thomas Peacock
    • , Tahel Ronel
    • , Mahdad Noursadeghi
    • , Virginia Turati
    • , Andrew J. S. Furness
    • , Andrew Georgiou
    • , Yien Ning Sophia Wong
    • , Assma Ben Aissa
    • , Mariana Werner Sunderland
    • , Mariam Jamal-Hanjani
    • , Selvaraju Veeriah
    • , Nicolai J. Birkbak
    • , Gareth A. Wilson
    • , Crispin T. Hiley
    • , Ehsan Ghorani
    • , José Afonso Guerra-Assunção
    • , Javier Herrero
    • , Tariq Enver
    • , Sine R. Hadrup
    • , Allan Hackshaw
    • , Karl S. Peggs
    • , Nicholas McGranahan
    • , Charles Swanton
    • , Sergio A. Quezada
    •  & Benny Chain
  • Article |

    A first-in-human, phase 1 dose-escalation trial demonstrates the safety and feasibility of autologous macrophage therapy in adults with liver cirrhosis.

    • Francesca Moroni
    • , Benjamin J. Dwyer
    • , Catriona Graham
    • , Chloe Pass
    • , Laura Bailey
    • , Lisa Ritchie
    • , Donna Mitchell
    • , Alison Glover
    • , Audrey Laurie
    • , Stuart Doig
    • , Emily Hargreaves
    • , Alasdair R. Fraser
    • , Marc L. Turner
    • , John D. M. Campbell
    • , Neil W. A. McGowan
    • , Jacqueline Barry
    • , Joanna K. Moore
    • , Peter C. Hayes
    • , Diana J. Leeming
    • , Mette J. Nielsen
    • , Kishwar Musa
    • , Jonathan A. Fallowfield
    •  & Stuart J. Forbes
  • Article |

    Expansion of human hematopoietic stem cells present in cord blood or bone marrow can be achieved by cell culture in a hydrogel, potentially facilitating clinical applications of hematopoietic cell transplantation.

    • Tao Bai
    • , Jianqiang Li
    • , Andrew Sinclair
    • , Suzan Imren
    • , Fabiola Merriam
    • , Fang Sun
    • , Mary Beth O’Kelly
    • , Cynthia Nourigat
    • , Priyesh Jain
    • , Jeffrey J. Delrow
    • , Ryan S. Basom
    • , Hsiang-Chieh Hung
    • , Peng Zhang
    • , Bowen Li
    • , Shelly Heimfeld
    • , Shaoyi Jiang
    •  & Colleen Delaney
  • Article |

    Single-cell proteomic and transcriptional profiling of atherosclerotic lesions from human carotid arteries reveals specific features of lesional T cells and macrophages associated with symptomatic disease.

    • Dawn M. Fernandez
    • , Adeeb H. Rahman
    • , Nicolas F. Fernandez
    • , Aleksey Chudnovskiy
    • , El-ad David Amir
    • , Letizia Amadori
    • , Nayaab S. Khan
    • , Christine K. Wong
    • , Roza Shamailova
    • , Christopher A. Hill
    • , Zichen Wang
    • , Romain Remark
    • , Jennifer R. Li
    • , Christian Pina
    • , Christopher Faries
    • , Ahmed J. Awad
    • , Noah Moss
    • , Johan L. M. Bjorkegren
    • , Seunghee Kim-Schulze
    • , Sacha Gnjatic
    • , Avi Ma’ayan
    • , J Mocco
    • , Peter Faries
    • , Miriam Merad
    •  & Chiara Giannarelli
  • Article |

    Analysis of monoclonal antibody responses to the Ebola virus vaccine rVSV-ZEBOV in human volunteers.

    • Stefanie A. Ehrhardt
    • , Matthias Zehner
    • , Verena Krähling
    • , Hadas Cohen-Dvashi
    • , Christoph Kreer
    • , Nadav Elad
    • , Henning Gruell
    • , Meryem S. Ercanoglu
    • , Philipp Schommers
    • , Lutz Gieselmann
    • , Ralf Eggeling
    • , Christine Dahlke
    • , Timo Wolf
    • , Nico Pfeifer
    • , Marylyn M. Addo
    • , Ron Diskin
    • , Stephan Becker
    •  & Florian Klein

Analysis

Resources

  • Resource |

    Rectal cancer organoids retain the pathological features of matched patient tumors and recapitulate clinical responses to chemoradiation.

    • Karuna Ganesh
    • , Chao Wu
    • , Kevin P. O’Rourke
    • , Bryan C. Szeglin
    • , Youyun Zheng
    • , Charles-Etienne Gabriel Sauvé
    • , Mohammad Adileh
    • , Isaac Wasserman
    • , Michael R. Marco
    • , Amanda S. Kim
    • , Maha Shady
    • , Francisco Sanchez-Vega
    • , Wouter R. Karthaus
    • , Helen H. Won
    • , Seo-Hyun Choi
    • , Raphael Pelossof
    • , Afsar Barlas
    • , Peter Ntiamoah
    • , Emmanouil Pappou
    • , Arthur Elghouayel
    • , James S. Strong
    • , Chin-Tung Chen
    • , Jennifer W. Harris
    • , Martin R. Weiser
    • , Garrett M. Nash
    • , Jose G. Guillem
    • , Iris H. Wei
    • , Richard N. Kolesnick
    • , Harini Veeraraghavan
    • , Eduardo J. Ortiz
    • , Iva Petkovska
    • , Andrea Cercek
    • , Katia O. Manova-Todorova
    • , Leonard B. Saltz
    • , Jessica A. Lavery
    • , Ronald P. DeMatteo
    • , Joan Massagué
    • , Philip B. Paty
    • , Rona Yaeger
    • , Xi Chen
    • , Sujata Patil
    • , Hans Clevers
    • , Michael F. Berger
    • , Scott W. Lowe
    • , Jinru Shia
    • , Paul B. Romesser
    • , Lukas E. Dow
    • , Julio Garcia-Aguilar
    • , Charles L. Sawyers
    •  & J. Joshua Smith
  • Resource |

    Genetic variants in the germ line modulate DNA methylation in tumors and contribute to the aggressiveness of prostate cancer.

    • Kathleen E. Houlahan
    • , Yu-Jia Shiah
    • , Alexander Gusev
    • , Jiapei Yuan
    • , Musaddeque Ahmed
    • , Anamay Shetty
    • , Susmita G. Ramanand
    • , Cindy Q. Yao
    • , Connor Bell
    • , Edward O’Connor
    • , Vincent Huang
    • , Michael Fraser
    • , Lawrence E. Heisler
    • , Julie Livingstone
    • , Takafumi N. Yamaguchi
    • , Alexandre Rouette
    • , Adrien Foucal
    • , Shadrielle Melijah G. Espiritu
    • , Ankit Sinha
    • , Michelle Sam
    • , Lee Timms
    • , Jeremy Johns
    • , Ada Wong
    • , Alex Murison
    • , Michèle Orain
    • , Valérie Picard
    • , Hélène Hovington
    • , Alain Bergeron
    • , Louis Lacombe
    • , Mathieu Lupien
    • , Yves Fradet
    • , Bernard Têtu
    • , John D. McPherson
    • , Bogdan Pasaniuc
    • , Thomas Kislinger
    • , Melvin L. K. Chua
    • , Mark M. Pomerantz
    • , Theodorus van der Kwast
    • , Matthew L. Freedman
    • , Ram S. Mani
    • , Housheng H. He
    • , Robert G. Bristow
    •  & Paul C. Boutros

Amendments & Corrections