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  • Could the specific glycosylation signatures associated with tumour cells be harnessed for immunotherapy purposes? In this Opinion, the authors propose that the tumour glyco-code may represent a novel immune checkpoint that could be targeted in the clinic.

    • Ernesto RodrÍguez
    • Sjoerd T. T. Schetters
    • Yvette van Kooyk
  • Normalization of the tumour vasculature can improve immune effector cell infiltration, leading to immunotherapy potentiation. In this Opinion article, Huanget al. propose that reciprocal regulation between tumour vascular normalization and immune reprogramming forms a positive feedback loop that can induce durable antitumour immunity within the tumour microenvironment.

    • Yuhui Huang
    • Betty Y. S. Kim
    • Wen Jiang
  • In this Opinion article, the authors consider how poverty and diet can shape the microbiota and immune health. They highlight how this contributes to the greater levels of chronic disease that are experienced by low-income individuals in high-income societies.

    • Christy A. Harrison
    • Douglas Taren
  • Carl Figdor and colleagues propose that delivering cancer immunotherapy in the context of engineered three-dimensional scaffolds may boost anticancer immunity. The synthetic scaffolds, which can be linked to immunomodulatory factors, can act as immune niches to support the priming and maintenance of antitumour immune responses.

    • Jorieke Weiden
    • Jurjen Tel
    • Carl G. Figdor
  • In this Opinion article, the authors discuss our growing appreciation of antigen-inexperienced memory T cell subsets. They focus on the development and functions of the recently described 'virtual memory' and 'innate memory' CD8+T cell populations, and propose a unified nomenclature for these subsets.

    • Jason T. White
    • Eric W. Cross
    • Ross M. Kedl
  • In this Opinion article, the authors discuss the limitations of categorizing tissue-resident macrophages based on their ontogeny. Instead, they propose that competition for a limited number of tissue niches may serve as a better framework for understanding the origins and functions of tissue macrophages.

    • Martin Guilliams
    • Charlotte L. Scott
  • Innate immune responses are triggered in response to the sensing of pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) by pattern recognition receptors (PRRs). An emerging idea is that inflammasome activation may also occur independently of PRR activation following a disturbance in cellular homeostasis. The authors explore this concept and the implications for chronic inflammatory disease in this Opinion article.

    • Adrian Liston
    • Seth L. Masters
  • A hypothesis is presented proposing that antibodies raised against commensal microorganisms shape the composition of the microbiota — through a process the authors call antibody-mediated immunoselection — and influence the overall health of the host.

    • Jason L. Kubinak
    • June L. Round
  • Clinical evidence, including results from randomized controlled clinical trials, strongly suggests that certain live vaccines can reduce all-cause mortality, most probably through protection against non-targeted pathogens. This Opinion article examines the potential immunological mechanisms underlying these effects.

    • Helen S. Goodridge
    • S. Sohail Ahmed
    • Christopher B. Wilson
  • Taking lessons from 'search theory', which is based on migration patterns of animals searching for prey, for example, Krummel and colleagues discuss the intrinsic and extrinsic forces that influence T cell motility patterns as the cell searches for antigen in lymphoid and non-lymphoid tissues.

    • Matthew F. Krummel
    • Frederic Bartumeus
    • Audrey Gérard
  • Improved treatments are needed for nearly all forms ofMycobacterium tuberculosisinfection. Adjunctive agents that target the host have the potential to shorten treatment duration, prevent resistance and reduce lung injury by promoting macrophage effector mechanisms and blocking mechanisms that cause lung destruction.

    • Robert S. Wallis
    • Richard Hafner
  • The discovery that patients with asthma can be dichotomized according to levels of type 2 inflammation, and hence their response to inhibitors of this pathway, promises to enhance our understanding of pathogenic mechanisms and personalized therapies.

    • John V. Fahy
  • The recent realization that the airways harbour a steady-state microbiota necessitates a shift in our understanding of respiratory health and disease, drawing from similarities with host–microorganism relationships in the intestines.

    • Benjamin J. Marsland
    • Eva S. Gollwitzer
  • Recent studies have shown that complement activation is not confined to the serum but also occurs within cellular compartments. This has led to an emerging understanding that complement components can intersect diverse cellular metabolic and effector pathways. Here, the authors propose that the different locations of complement activation dictate its diverse functions.

    • Martin Kolev
    • Gaelle Le Friec
    • Claudia Kemper
  • This Opinion article proposes that higher-order protein complexes — referred to as supramolecular organizing centres (SMOCs) — form on specific organelles by nucleated polymerization downstream of innate immune receptors to amplify the signal and reach a response threshold.

    • Jonathan C. Kagan
    • Venkat Giri Magupalli
    • Hao Wu
  • In this Opinion article, the authors discuss how the induction of regulated cell death and inflammatory pathways may lead to an auto-amplification loop that causes tissue damage and organ failure. They propose that targeting both processes could be useful for treating a broad range of clinical conditions with an inflammatory basis.

    • Andreas Linkermann
    • Brent R. Stockwell
    • Hans-Joachim Anders
  • Chronic viral infections and malignant tumours are associated with the development of T cells that have an 'exhausted' phenotype and that are thought to be severely functionally impaired. In this Opinion article, the authors propose that the exhausted phenotype is actually a functional adaptation to cause minimal tissue damage while still mediating a critical level of pathogen control.

    • Daniel E. Speiser
    • Daniel T. Utzschneider
    • Dietmar Zehn