Volume 25 Issue 3, March 2019

Volume 25 Issue 3

Focus on Cancer Therapy

Reducing the burden of cancer remains a critical global health challenge. Ahead of the 2019 meeting of the American Association of Cancer Research, we bring our readers a special Focus on Cancer Therapy that highlights opportunities and challenges in our understanding of the disease, the development of new therapeutic approaches and the need for improved care and early diagnosis. The cover image is an artistic rendition of the combination of multiplex immunofluorescence and CyTOF analyses of glioblastoma samples from patients treated with neoadjuvant pembrolizumab, reported by Rob Prins and colleagues in this issue.

Image credit: Aaron Mochizuki. Cover design: Erin Dewalt

Editorial

  • Editorial |

    Cancer surveillance programs have reported a global downward trend in cancer mortality rates for most common tumor types. However, startling geographic inequalities exist, and some cancers continue to pose a challenge. Ensuring global access to high-quality diagnostic and treatment approaches is needed to make decreasing cancer deaths a more widespread trend.

News Feature

Turning Points

  • Turning Points |

    Georgina V. Long is co-medical director of Melanoma Institute Australia and Chair of Melanoma Medical Oncology and Translational Research. She is the first woman president of the Society for Melanoma Research.

    • Georgina V. Long

Research Highlights

News & Views

  • News & Views |

    Transcriptional signatures and immune cell infiltrates associated with immune activation distinguish patients with glioblastoma who initially respond to immune checkpoint blockade from those who do not.

    • Hirotaka Ito
    • , Hiroshi Nakashima
    •  & E. Antonio Chiocca
  • News & Views |

    Non-invasive prenatal diagnostics allow for the successful identification of paternally inherited and de novo mongenic diseases using circulating cell-free DNA.

    • Nancy B. Spinner
    •  & Ian D. Krantz
  • News & Views |

    Application of immunoprofiling of human peripheral blood samples from an aging cohort identifies changes in the immune system that inform our understanding of age-associated complex diseases.

    • Soumya Raychaudhuri
    •  & Rajat M. Gupta
  • News & Views |

    The analysis of autopsy material from individuals with multiple sclerosis with single-cell transcriptomics and 14C carbon dating calls for a reevaluation of mature oligodendrocytes in myelin repair.

    • Klaus-Armin Nave
    •  & Hannelore Ehrenreich

Review Articles

Brief Communications

  • Brief Communication |

    AAV-mediated CRISPR/Cas9 therapy extends life span and ameliorates disease-related phenotypes in a mouse model of Hutchinson–Gilford progeria syndrome.

    • Olaya Santiago-Fernández
    • , Fernando G. Osorio
    • , Víctor Quesada
    • , Francisco Rodríguez
    • , Sammy Basso
    • , Daniel Maeso
    • , Loïc Rolas
    • , Anna Barkaway
    • , Sussan Nourshargh
    • , Alicia R. Folgueras
    • , José M. P. Freije
    •  & Carlos López-Otín

Letters

  • Letter |

    In the mdx mouse model of Duchenne muscular dystrophy, single intravenous administration of AAV-CRISPR–Cas9 vectors provides efficient genome editing and restoration of dystrophin expression lasting for one year.

    • Christopher E. Nelson
    • , Yaoying Wu
    • , Matthew P. Gemberling
    • , Matthew L. Oliver
    • , Matthew A. Waller
    • , Joel D. Bohning
    • , Jacqueline N. Robinson-Hamm
    • , Karen Bulaklak
    • , Ruth M. Castellanos Rivera
    • , Joel H. Collier
    • , Aravind Asokan
    •  & Charles A. Gersbach
  • Letter |

    A natural language processing system can support physicians in diagnostic assessments by extracting clinical information from electronic medical records to accurately predict diagnosis in pediatric patients.

    • Huiying Liang
    • , Brian Y. Tsui
    • , Hao Ni
    • , Carolina C. S. Valentim
    • , Sally L. Baxter
    • , Guangjian Liu
    • , Wenjia Cai
    • , Daniel S. Kermany
    • , Xin Sun
    • , Jiancong Chen
    • , Liya He
    • , Jie Zhu
    • , Pin Tian
    • , Hua Shao
    • , Lianghong Zheng
    • , Rui Hou
    • , Sierra Hewett
    • , Gen Li
    • , Ping Liang
    • , Xuan Zang
    • , Zhiqi Zhang
    • , Liyan Pan
    • , Huimin Cai
    • , Rujuan Ling
    • , Shuhua Li
    • , Yongwang Cui
    • , Shusheng Tang
    • , Hong Ye
    • , Xiaoyan Huang
    • , Waner He
    • , Wenqing Liang
    • , Qing Zhang
    • , Jianmin Jiang
    • , Wei Yu
    • , Jianqun Gao
    • , Wanxing Ou
    • , Yingmin Deng
    • , Qiaozhen Hou
    • , Bei Wang
    • , Cuichan Yao
    • , Yan Liang
    • , Shu Zhang
    • , Yaou Duan
    • , Runze Zhang
    • , Sarah Gibson
    • , Charlotte L. Zhang
    • , Oulan Li
    • , Edward D. Zhang
    • , Gabriel Karin
    • , Nathan Nguyen
    • , Xiaokang Wu
    • , Cindy Wen
    • , Jie Xu
    • , Wenqin Xu
    • , Bochu Wang
    • , Winston Wang
    • , Jing Li
    • , Bianca Pizzato
    • , Caroline Bao
    • , Daoman Xiang
    • , Wanting He
    • , Suiqin He
    • , Yugui Zhou
    • , Weldon Haw
    • , Michael Goldbaum
    • , Adriana Tremoulet
    • , Chun-Nan Hsu
    • , Hannah Carter
    • , Long Zhu
    • , Kang Zhang
    •  & Huimin Xia
  • Letter |

    A non-invasive prenatal test utilizing cell-free DNA simultaneously detects mutations in 30 genes frequently associated with dominant monogenic diseases and demonstrates high accuracy in human clinical samples.

    • Jinglan Zhang
    • , Jianli Li
    • , Jennifer B. Saucier
    • , Yanming Feng
    • , Yanjun Jiang
    • , Jefferson Sinson
    • , Anne K. McCombs
    • , Eric S. Schmitt
    • , Sandra Peacock
    • , Stella Chen
    • , Hongzheng Dai
    • , Xiaoyan Ge
    • , Guoli Wang
    • , Chad A. Shaw
    • , Hui Mei
    • , Amy Breman
    • , Fan Xia
    • , Yaping Yang
    • , Anne Purgason
    • , Alan Pourpak
    • , Zhao Chen
    • , Xia Wang
    • , Yue Wang
    • , Shashikant Kulkarni
    • , Kwong Wai Choy
    • , Ronald J. Wapner
    • , Ignatia B. Van den Veyver
    • , Arthur Beaudet
    • , Sheetal Parmar
    • , Lee-Jun Wong
    •  & Christine M. Eng
  • Letter |

    Specific members of the gut microbiota are critical for regulating allergic responses to dietary antigens.

    • Taylor Feehley
    • , Catherine H. Plunkett
    • , Riyue Bao
    • , Sung Min Choi Hong
    • , Elliot Culleen
    • , Pedro Belda-Ferre
    • , Evelyn Campbell
    • , Rosita Aitoro
    • , Rita Nocerino
    • , Lorella Paparo
    • , Jorge Andrade
    • , Dionysios A. Antonopoulos
    • , Roberto Berni Canani
    •  & Cathryn R. Nagler
  • Letter |

    Neoadjuvant PD-1 blockade in patients with resectable melanoma followed by adjuvant maintenance results in early immunological effects driving clinical benefit and reveals transcriptional and genomic mechanisms of response.

    • Alexander C. Huang
    • , Robert J. Orlowski
    • , Xiaowei Xu
    • , Rosemarie Mick
    • , Sangeeth M. George
    • , Patrick K. Yan
    • , Sasikanth Manne
    • , Adam A. Kraya
    • , Bradley Wubbenhorst
    • , Liza Dorfman
    • , Kurt D’Andrea
    • , Brandon M. Wenz
    • , Shujing Liu
    • , Lakshmi Chilukuri
    • , Andrew Kozlov
    • , Mary Carberry
    • , Lydia Giles
    • , Melanie W. Kier
    • , Felix Quagliarello
    • , Suzanne McGettigan
    • , Kristin Kreider
    • , Lakshmanan Annamalai
    • , Qing Zhao
    • , Robin Mogg
    • , Wei Xu
    • , Wendy M. Blumenschein
    • , Jennifer H. Yearley
    • , Gerald P. Linette
    • , Ravi K. Amaravadi
    • , Lynn M. Schuchter
    • , Ramin S. Herati
    • , Bertram Bengsch
    • , Katherine L. Nathanson
    • , Michael D. Farwell
    • , Giorgos C. Karakousis
    • , E. John Wherry
    •  & Tara C. Mitchell
  • Letter |

    Genomic, transcriptomic, and microenvironmental analyses of samples from patients with glioblastoma treated with nivolumab or pembrolizumab identifies features associated with treatment response that may help in refining patient stratification.

    • Junfei Zhao
    • , Andrew X. Chen
    • , Robyn D. Gartrell
    • , Andrew M. Silverman
    • , Luis Aparicio
    • , Tim Chu
    • , Darius Bordbar
    • , David Shan
    • , Jorge Samanamud
    • , Aayushi Mahajan
    • , Ioan Filip
    • , Rose Orenbuch
    • , Morgan Goetz
    • , Jonathan T. Yamaguchi
    • , Michael Cloney
    • , Craig Horbinski
    • , Rimas V. Lukas
    • , Jeffrey Raizer
    • , Ali I. Rae
    • , Jinzhou Yuan
    • , Peter Canoll
    • , Jeffrey N. Bruce
    • , Yvonne M. Saenger
    • , Peter Sims
    • , Fabio M. Iwamoto
    • , Adam M. Sonabend
    •  & Raul Rabadan
  • Letter |

    Neoadjuvant nivolumab treatment in patients with glioblastoma induces intratumoral immune activation and underscores the need for rationale-based combination approaches for improving clinical responses.

    • Kurt A. Schalper
    • , Maria E. Rodriguez-Ruiz
    • , Ricardo Diez-Valle
    • , Alvaro López-Janeiro
    • , Angelo Porciuncula
    • , Miguel A. Idoate
    • , Susana Inogés
    • , Carlos de Andrea
    • , Ascensión López-Diaz de Cerio
    • , Sonia Tejada
    • , Pedro Berraondo
    • , Franz Villarroel-Espindola
    • , Jungmin Choi
    • , Alfonso Gúrpide
    • , Miriam Giraldez
    • , Iosune Goicoechea
    • , Jaime Gallego Perez-Larraya
    • , Miguel F. Sanmamed
    • , Jose L. Perez-Gracia
    •  & Ignacio Melero

Articles

  • Article |

    Neoadjuvant pembrolizumab promotes a survival benefit with intratumoral and systemic immune responses in patients with recurrent glioblastoma.

    • Timothy F. Cloughesy
    • , Aaron Y. Mochizuki
    • , Joey R. Orpilla
    • , Willy Hugo
    • , Alexander H. Lee
    • , Tom B. Davidson
    • , Anthony C. Wang
    • , Benjamin M. Ellingson
    • , Julie A. Rytlewski
    • , Catherine M. Sanders
    • , Eric S. Kawaguchi
    • , Lin Du
    • , Gang Li
    • , William H. Yong
    • , Sarah C. Gaffey
    • , Adam L. Cohen
    • , Ingo K. Mellinghoff
    • , Eudocia Q. Lee
    • , David A. Reardon
    • , Barbara J. O’Brien
    • , Nicholas A. Butowski
    • , Phioanh L. Nghiemphu
    • , Jennifer L. Clarke
    • , Isabel C. Arrillaga-Romany
    • , Howard Colman
    • , Thomas J. Kaley
    • , John F. de Groot
    • , Linda M. Liau
    • , Patrick Y. Wen
    •  & Robert M. Prins
  • Article |

    An integrated high-dimensional measurement of immune age describes a person’s immune status better than chronological age and predicts all-cause mortality.

    • Ayelet Alpert
    • , Yishai Pickman
    • , Michael Leipold
    • , Yael Rosenberg-Hasson
    • , Xuhuai Ji
    • , Renaud Gaujoux
    • , Hadas Rabani
    • , Elina Starosvetsky
    • , Ksenya Kveler
    • , Steven Schaffert
    • , David Furman
    • , Oren Caspi
    • , Uri Rosenschein
    • , Purvesh Khatri
    • , Cornelia L. Dekker
    • , Holden T. Maecker
    • , Mark M. Davis
    •  & Shai S. Shen-Orr
  • Article |

    ApoE is a direct checkpoint inhibitor of unresolvable inflammation in neurodegenerative and cardiovascular diseases

    • Changjun Yin
    • , Susanne Ackermann
    • , Zhe Ma
    • , Sarajo K. Mohanta
    • , Chuankai Zhang
    • , Yuanfang Li
    • , Sandor Nietzsche
    • , Martin Westermann
    • , Li Peng
    • , Desheng Hu
    • , Sai Vineela Bontha
    • , Prasad Srikakulapu
    • , Michael Beer
    • , Remco T. A. Megens
    • , Sabine Steffens
    • , Markus Hildner
    • , Luke D. Halder
    • , Hans-Henning Eckstein
    • , Jaroslav Pelisek
    • , Jochen Herms
    • , Sigrun Roeber
    • , Thomas Arzberger
    • , Anna Borodovsky
    • , Livia Habenicht
    • , Christoph J. Binder
    • , Christian Weber
    • , Peter F. Zipfel
    • , Christine Skerka
    •  & Andreas J. R. Habenicht
  • Article |

    Defects in the regulation of leptin gene expression can lead to a hypoleptinemic, leptin-responsive form of obesity.

    • Olof S. Dallner
    • , Jill M. Marinis
    • , Yi-Hsueh. Lu
    • , Kivanc Birsoy
    • , Emory Werner
    • , Gulya Fayzikhodjaeva
    • , Brian D. Dill
    • , Henrik Molina
    • , Arden Moscati
    • , Zoltán Kutalik
    • , Pedro Marques-Vidal
    • , Tuomas O. Kilpeläinen
    • , Niels Grarup
    • , Allan Linneberg
    • , Yinxin Zhang
    • , Roger Vaughan
    • , Ruth J. F. Loos
    • , Mitchell A. Lazar
    •  & Jeffrey M. Friedman

Resources

  • Resource |

    A multi-omics survey of progressive compared to regressive carcinoma in situ lesions provides a molecular map of early lung cancer development.

    • Vitor H. Teixeira
    • , Christodoulos P. Pipinikas
    • , Adam Pennycuick
    • , Henry Lee-Six
    • , Deepak Chandrasekharan
    • , Jennifer Beane
    • , Tiffany J. Morris
    • , Anna Karpathakis
    • , Andrew Feber
    • , Charles E. Breeze
    • , Paschalis Ntolios
    • , Robert E. Hynds
    • , Mary Falzon
    • , Arrigo Capitanio
    • , Bernadette Carroll
    • , Pascal F. Durrenberger
    • , Georgia Hardavella
    • , James M. Brown
    • , Andy G. Lynch
    • , Henry Farmery
    • , Dirk S. Paul
    • , Rachel C. Chambers
    • , Nicholas McGranahan
    • , Neal Navani
    • , Ricky M. Thakrar
    • , Charles Swanton
    • , Stephan Beck
    • , Phillip Jeremy George
    • , Avrum Spira
    • , Peter J. Campbell
    • , Christina Thirlwell
    •  & Sam M. Janes

Amendments & Corrections