Collection |

Nobel Prize in Physiology or Medicine 2018

The 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation”. Their pioneering work on the CTLA4 and PD1 immune checkpoints revealed that these pathways act as so-called ‘brakes’ on the immune system, and showed that inhibition of these checkpoint pathways allows T cells to more effectively eradicate cancer cells. This research laid the foundation for the clinical development of immune checkpoint inhibitors, which have dramatically improved outcomes for many people with cancer.

This Collection presents research, review, news and comment articles from Nature Research to celebrate the award. The collection content is editorially independent and the sole responsibility of Springer Nature.

Core collection – free

  • Nature Reviews Cancer | Review Article

    Insights into the effects of targeted therapies, conventional chemotherapy and radiation therapy, on the induction of antitumour immunity will help to advance the design of combination strategies that increase the rate of complete and durable clinical responses in patients.

    • Philip Gotwals
    • , Scott Cameron
    • , Daniela Cipolletta
    • , Viviana Cremasco
    • , Adam Crystal
    • , Becker Hewes
    • , Britta Mueller
    • , Sonia Quaratino
    • , Catherine Sabatos-Peyton
    • , Lilli Petruzzelli
    • , Jeffrey A. Engelman
    •  &  Glenn Dranoff
  • Nature Reviews Clinical Oncology | Review Article

    Patients receiving anticancer therapies based on immune-checkpoint blockade (ICB) often experience clinical benefits from such treatments, but unconventional patterns of response can be observed, emphasizing the importance of using a specific approach to evaluating responses to immunotherapy. Herein, the authors review the biological mechanisms underlying the response patterns associated with ICB, describe strategies for the assessments of such responses, and highlight the ongoing efforts to identify biomarkers to guide treatment with ICB.

    • Mizuki Nishino
    • , Nikhil H. Ramaiya
    • , Hiroto Hatabu
    •  &  F. Stephen Hodi
  • Nature Reviews Drug Discovery | Outlook

    Immuno-oncology has become the fastest-growing area in the pharmaceutical industry. In this Perspective, Hoos provides an overview of the history of immuno-oncology and investigates the factors that have led to its success. Moreover, he discusses the three generations of immunotherapies that have been developed since 2011 and provides an outlook to the future directions of drug discovery and development in immuno-oncology.

    • Axel Hoos
  • Nature Reviews Immunology | Perspective

    This Timeline looks back at the past 60 years of fundamental research into the mechanisms of T cell-mediated cytotoxicity, which has culminated in recent interest in the therapeutic manipulation of cytotoxic T cell responses for cancer immunotherapy.

    • Pierre Golstein
    •  &  Gillian M. Griffiths
  • Nature Medicine | Brief Communication

    Prostate cancer is refractory to anti-CTLA-4 therapy, but the reason why is unclear. Padmanee Sharma and colleagues report that the inhibitory molecule VISTA, which negatively regulates T cells, is upregulated on macrophages in prostate tumors that have been treated with anti-CTLA-4 and may play a role in resistance to this immunotherapy.

    • Jianjun Gao
    • , John F Ward
    • , Curtis A Pettaway
    • , Lewis Z Shi
    • , Sumit K Subudhi
    • , Luis M Vence
    • , Hao Zhao
    • , Jianfeng Chen
    • , Hong Chen
    • , Eleni Efstathiou
    • , Patricia Troncoso
    • , James P Allison
    • , Christopher J Logothetis
    • , Ignacio I Wistuba
    • , Manuel A Sepulveda
    • , Jingjing Sun
    • , Jennifer Wargo
    • , Jorge Blando
    •  &  Padmanee Sharma

From the winners

  • Nature Medicine | Commentary

    Successful translation of modern molecular immunology into effective cancer immunotherapy is threatened by regulatory barriers and challenges to the development of novel agents and combinatorial strategies through effective public-private partnerships. For its promise to be fully realized, both the National Cancer Institute and Food and Drug Administration must take active steps to help academic investigators and companies jointly navigate the pathways from laboratory to clinic.

    • Drew Pardoll
    •  &  James Allison
  • Nature Reviews Cancer | Opinion

    The US Food and Drug Administration (FDA) recently approved the immunotherapy agents sipuleucel-T and ipilimumab for the treatment of metastatic prostate cancer and melanoma, respectively. This Opinion article discusses how immunotherapy might be improved by understanding the mechanisms that are responsible for clinical benefit, identifying biomarkers that predict response or toxicity and developing combination therapies.

    • Padmanee Sharma
    • , Klaus Wagner
    • , Jedd D. Wolchok
    •  &  James P. Allison
  • Nature Communications | Article | open

    Programmed Death ligand-1 (PD-L1) protein mediates immune suppression in cancer. Here, the authors show that in breast cancer, PD-L1 expression can be up regulated post-translationally by glycosylation, which in turn acts through inhibiting GSK3β-mediated PD-L1 degradation.

    • Chia-Wei Li
    • , Seung-Oe Lim
    • , Weiya Xia
    • , Heng-Huan Lee
    • , Li-Chuan Chan
    • , Chu-Wei Kuo
    • , Kay-Hooi Khoo
    • , Shih-Shin Chang
    • , Jong-Ho Cha
    • , Taewan Kim
    • , Jennifer L. Hsu
    • , Yun Wu
    • , Jung-Mao Hsu
    • , Hirohito Yamaguchi
    • , Qingqing Ding
    • , Yan Wang
    • , Jun Yao
    • , Cheng-Chung Lee
    • , Hsing-Ju Wu
    • , Aysegul A. Sahin
    • , James P. Allison
    • , Dihua Yu
    • , Gabriel N. Hortobagyi
    •  &  Mien-Chie Hung
  • Nature Communications | Article | open

    Combination therapy with α-CTLA-4 and α-PD-1 is showing improved therapeutic effects in clinical trials. Here, the authors report that mechanistically in bladder cancer such effect depends upon an upregulation of T cell activity mediated by the IL-7/IL-7R and IFN-γ/IFN-γR signalling pathways.

    • Lewis Zhichang Shi
    • , Tihui Fu
    • , Baoxiang Guan
    • , Jianfeng Chen
    • , Jorge M. Blando
    • , James P. Allison
    • , Liangwen Xiong
    • , Sumit K. Subudhi
    • , Jianjun Gao
    •  &  Padmanee Sharma

Research

  • Nature | Letter

    A carcinogen-induced mouse tumour model is used here to show that mutant tumour-specific antigens are targets for CD8+ T-cell responses, mediating tumour regression after checkpoint blockade immunotherapy, and that these antigens can be used effectively in therapeutic vaccines; this advance potentially opens the door to personalized cancer vaccines.

    • Matthew M. Gubin
    • , Xiuli Zhang
    • , Heiko Schuster
    • , Etienne Caron
    • , Jeffrey P. Ward
    • , Takuro Noguchi
    • , Yulia Ivanova
    • , Jasreet Hundal
    • , Cora D. Arthur
    • , Willem-Jan Krebber
    • , Gwenn E. Mulder
    • , Mireille Toebes
    • , Matthew D. Vesely
    • , Samuel S. K. Lam
    • , Alan J. Korman
    • , James P. Allison
    • , Gordon J. Freeman
    • , Arlene H. Sharpe
    • , Erika L. Pearce
    • , Ton N. Schumacher
    • , Ruedi Aebersold
    • , Hans-Georg Rammensee
    • , Cornelis J. M. Melief
    • , Elaine R. Mardis
    • , William E. Gillanders
    • , Maxim N. Artyomov
    •  &  Robert D. Schreiber
  • Nature | Letter

    The dynamics of T-cell responses are investigated in tumour tissue from patients with advanced melanoma who were treated with a PD-1-blocking monoclonal antibody, revealing that clinical efficacy of the treatment correlates with increased frequencies of pre-existing CD8+ T cells and PD-1 and PD-L1 expression.

    • Paul C. Tumeh
    • , Christina L. Harview
    • , Jennifer H. Yearley
    • , I. Peter Shintaku
    • , Emma J. M. Taylor
    • , Lidia Robert
    • , Bartosz Chmielowski
    • , Marko Spasic
    • , Gina Henry
    • , Voicu Ciobanu
    • , Alisha N. West
    • , Manuel Carmona
    • , Christine Kivork
    • , Elizabeth Seja
    • , Grace Cherry
    • , Antonio J. Gutierrez
    • , Tristan R. Grogan
    • , Christine Mateus
    • , Gorana Tomasic
    • , John A. Glaspy
    • , Ryan O. Emerson
    • , Harlan Robins
    • , Robert H. Pierce
    • , David A. Elashoff
    • , Caroline Robert
    •  &  Antoni Ribas
  • Nature | Letter

    Clinical and correlative biomarker results from a phase 1 clinical trial in patients with different solid tumours are presented; the findings indicate that PD-L1 expression on tumour-infiltrating immune cells is associated with clinical response to MPDL3280A (anti-PD-L1).

    • Roy S. Herbst
    • , Jean-Charles Soria
    • , Marcin Kowanetz
    • , Gregg D. Fine
    • , Omid Hamid
    • , Michael S. Gordon
    • , Jeffery A. Sosman
    • , David F. McDermott
    • , John D. Powderly
    • , Scott N. Gettinger
    • , Holbrook E. K. Kohrt
    • , Leora Horn
    • , Donald P. Lawrence
    • , Sandra Rost
    • , Maya Leabman
    • , Yuanyuan Xiao
    • , Ahmad Mokatrin
    • , Hartmut Koeppen
    • , Priti S. Hegde
    • , Ira Mellman
    • , Daniel S. Chen
    •  &  F. Stephen Hodi
  • Nature | Letter

    The results of a clinical phase I study in metastatic urothelial bladder cancer treated with the MPDL3280A antibody show that expression of PD-L1 on tumour-infiltrating immune cells is relevant for the therapeutic response.

    • Thomas Powles
    • , Joseph Paul Eder
    • , Gregg D. Fine
    • , Fadi S. Braiteh
    • , Yohann Loriot
    • , Cristina Cruz
    • , Joaquim Bellmunt
    • , Howard A. Burris
    • , Daniel P. Petrylak
    • , Siew-leng Teng
    • , Xiaodong Shen
    • , Zachary Boyd
    • , Priti S. Hegde
    • , Daniel S. Chen
    •  &  Nicholas J. Vogelzang
  • Nature | Letter

    A combination of TGFβ inhibition and checkpoint-inhibition therapy provokes a potent cytotoxic response against metastatic tumours derived from colorectal cancers in mice.

    • Daniele V. F. Tauriello
    • , Sergio Palomo-Ponce
    • , Diana Stork
    • , Antonio Berenguer-Llergo
    • , Jordi Badia-Ramentol
    • , Mar Iglesias
    • , Marta Sevillano
    • , Sales Ibiza
    • , Adrià Cañellas
    • , Xavier Hernando-Momblona
    • , Daniel Byrom
    • , Joan A. Matarin
    • , Alexandre Calon
    • , Elisa I. Rivas
    • , Angel R. Nebreda
    • , Antoni Riera
    • , Camille Stephan-Otto Attolini
    •  &  Eduard Batlle
  • Nature | Letter

    In humans, TGFβ signalling is associated with lack of response to immunotherapy in immune-excluded tumours; in mouse models of this immune phenotype, robust tumour infiltration by T cells and tumour regression are observed only when checkpoint inhibition is combined with inhibition of TGFβ signalling.

    • Sanjeev Mariathasan
    • , Shannon J. Turley
    • , Dorothee Nickles
    • , Alessandra Castiglioni
    • , Kobe Yuen
    • , Yulei Wang
    • , Edward E. Kadel III
    • , Hartmut Koeppen
    • , Jillian L. Astarita
    • , Rafael Cubas
    • , Suchit Jhunjhunwala
    • , Romain Banchereau
    • , Yagai Yang
    • , Yinghui Guan
    • , Cecile Chalouni
    • , James Ziai
    • , Yasin Şenbabaoğlu
    • , Stephen Santoro
    • , Daniel Sheinson
    • , Jeffrey Hung
    • , Jennifer M. Giltnane
    • , Andrew A. Pierce
    • , Kathryn Mesh
    • , Steve Lianoglou
    • , Johannes Riegler
    • , Richard A. D. Carano
    • , Pontus Eriksson
    • , Mattias Höglund
    • , Loan Somarriba
    • , Daniel L. Halligan
    • , Michiel S. van der Heijden
    • , Yohann Loriot
    • , Jonathan E. Rosenberg
    • , Lawrence Fong
    • , Ira Mellman
    • , Daniel S. Chen
    • , Marjorie Green
    • , Christina Derleth
    • , Gregg D. Fine
    • , Priti S. Hegde
    • , Richard Bourgon
    •  &  Thomas Powles

Reviews and Comment

  • Nature Reviews Cancer | Viewpoint

    Many patients have now received various types of immunotherapy, so we asked three scientists to give their views on whether acquired resistance to immunotherapy exists in patients and the future challenges posed by immunotherapy.

    • Nicholas P. Restifo
    • , Mark J. Smyth
    •  &  Alexandra Snyder
  • Nature Reviews Clinical Oncology | Review Article

    The aim of immunotherapy is to treat cancer by enabling the immune system to attack the tumour. In the past decade, remarkable results have been obtained in clinical trials with immunotherapy for patients with advanced-stage cancer. Two types of immunotherapy have been used in the majority of trials conducted in the past decade: immune cell-targeted antibody therapy and adoptive cellular therapy. Herein, the latest advances in both modalities are discussed, including settings for which testing combination strategies and 'armoured' CAR T cells are recommended.

    • Danny N. Khalil
    • , Eric L. Smith
    • , Renier J. Brentjens
    •  &  Jedd D. Wolchok
  • Nature Medicine | Review Article

    The tumor immune microenvironment influences tumor progression and response to immunotherapy; its further characterization will improve therapeutic outcome.

    • Mikhail Binnewies
    • , Edward W. Roberts
    • , Kelly Kersten
    • , Vincent Chan
    • , Douglas F. Fearon
    • , Miriam Merad
    • , Lisa M. Coussens
    • , Dmitry I. Gabrilovich
    • , Suzanne Ostrand-Rosenberg
    • , Catherine C. Hedrick
    • , Robert H. Vonderheide
    • , Mikael J. Pittet
    • , Rakesh K. Jain
    • , Weiping Zou
    • , T. Kevin Howcroft
    • , Elisa C. Woodhouse
    • , Robert A. Weinberg
    •  &  Matthew F. Krummel
  • Nature Reviews Immunology | Review Article

    In this Review, the authors detail the complex expression patterns and regulation of programmed cell death protein 1 (PD1) and its ligands. The authors focus on the importance of understanding these pathways in order to optimize the efficiency and safety of immune checkpoint blockade in patients.

    • Arlene H. Sharpe
    •  &  Kristen E. Pauken
  • Nature Reviews Immunology | Review Article

    Recent clinical trials have shown that blocking immune checkpoint molecules can boost antitumour immune responses. In this Review, the authors consider whether targeting these pathways could also be used to combat a range of infectious diseases, such as malaria, tuberculosis and chronic viral infections.

    • Michelle N. Wykes
    •  &  Sharon R. Lewin
  • Nature Reviews Disease Primers | Primer

    Urothelial bladder cancer is one of the most common, and most deadly, malignant diseases worldwide. This Primer summarizes the current epidemiological and outcome data of patients with this disease, as well as describing how new molecular subtyping strategies might improve patient care in the future.

    • Oner Sanli
    • , Jakub Dobruch
    • , Margaret A. Knowles
    • , Maximilian Burger
    • , Mehrdad Alemozaffar
    • , Matthew E. Nielsen
    •  &  Yair Lotan

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