• Immunity · Jun 2016

    Review

    Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors.

    • Jonathan M Pitt, Marie Vétizou, Romain Daillère, María Paula Roberti, Takahiro Yamazaki, Bertrand Routy, Patricia Lepage, BonecaIvo GompertsIGUnit of Biology and Genetics of the Bacterial Cell Wall, Institut Pasteur, 75015 Paris, France; Equipe Avenir, INSERM, 75015 Paris, France., Mathias Chamaillard, Guido Kroemer, and Laurence Zitvogel.
    • Institut de Cancérologie, Gustave Roussy Cancer Campus, 94800 Villejuif, France; INSERM U1015, 94800 Villejuif, France; Faculté de Médecine, Université Paris Sud, Université Paris-Saclay, 94276 Le Kremlin Bicêtre, France.
    • Immunity. 2016 Jun 21; 44 (6): 1255-69.

    AbstractInhibition of immune regulatory checkpoints, such as CTLA-4 and the PD-1-PD-L1 axis, is at the forefront of immunotherapy for cancers of various histological types. However, such immunotherapies fail to control neoplasia in a significant proportion of patients. Here, we review how a range of cancer-cell-autonomous cues, tumor-microenvironmental factors, and host-related influences might account for the heterogeneous responses and failures often encountered during therapies using immune-checkpoint blockade. Furthermore, we describe the emerging evidence of how the strong interrelationship between the immune system and the host microbiota can determine responses to cancer therapies, and we introduce a concept by which prior or concomitant modulation of the gut microbiome could optimize therapeutic outcomes upon immune-checkpoint blockade.Copyright © 2016 Elsevier Inc. All rights reserved.

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