Review Articles in 2019

Organoid technology has emerged as a powerful tool to maintain epithelial cells in a near-native state that can be used to better understand the interactions between epithelial cells and the immune system in tissue development, homeostasis, infection and cancer.

Immune cells and neural cells interact in numerous tissues and organs and can have local and far-reaching physiological effects. Understanding these intimate bidirectional interactions is providing insight into the gut–brain axis, as well as the maternal gut–fetal brain axis.

The authors discuss the formation of two main ‘walls’ of B cell memory to protect against pathogen reinfection. The first wall comprises high-affinity antibodies produced by long-lived plasma cells, while the second wall is formed by memory B cells.

Clearing away dead cells — a process known as efferocytosis — is crucial for normal tissue homeostasis and is impaired in several pathological processes. This Review describes new insights into how efferocytes deal with the engulfed dead cell cargo, how efferocytosis supports the resolution of inflammation and how this understanding is informing new therapeutic strategies.

Therapies based on adoptive cellular transfer of regulatory T (T_reg) cells are currently undergoing clinical trials for autoimmune diseases, graft-versus-host disease and the prevention of transplant rejection. This Review provides an overview of T_reg cell biology and discusses the latest approaches to enhance T_reg cells for therapeutic purposes.

This Review by Handel and colleagues focuses on how simulation modelling can be used to interrogate the immune system. The authors provide an overview of different model types and encourage immunologists to build their own models.

Recent studies using single-cell genomic technologies and in vivo fate mapping have shown that thymic epithelial cells are far more heterogeneous than previously thought, comprising multiple subpopulations with distinct molecular and functional characteristics.

The gasdermin family of proteins has the capacity to form pores in the membrane, causing a pro-inflammatory lytic type of cell death called pyroptosis, This Review provides a comprehensive overview of the gasdermin family, the mechanisms that control their activation and their role in inflammatory disorders and cancer.

The co-inhibitory receptor TIM3 can serve as a marker of exhausted T cells. Here, the authors investigate the biology of TIM3, discussing its various ligands, signalling pathways and association with human disease. They also provide an overview of emerging clinical data regarding its potential as an anticancer target in combination with PD1 blockade.

This Review focuses on the cytomegaloviruses and the sophisticated strategies they have evolved to evade immune recognition. The authors suggest a better appreciation of these pathways could have clinical implications beyond antiviral immunity, for instance in understanding immune evasion in cancer.

Understanding why some patients and not others respond to immune checkpoint blockade for cancer is crucial for extending benefit from this therapy. Here the authors describe how tumour cells can resist immune checkpoint blockade, for example, by resistance to interferon signalling and through immune-evasive oncogenic signalling pathways.

Host-derived molecules, the so-called damage-associated molecular patterns (DAMPs), can induce sterile inflammation. This Review provides an overview of DAMP-sensing receptors, discusses the crosstalk between these receptors and explores their role in disease.

The authors consider the inflammatory basis of type 1 and type 2 diabetes. In particular, they focus on the role of IL-1β in both diseases and discuss the feasibility of targeting innate immune mechanisms in the clinic.

There is growing interest in harnessing dendritic cells for cancer immunotherapy. Here the authors describe the roles of dendritic cells in the tumour microenvironment and the different strategies that are being developed to target these cells in the clinic.

Recent advances in single-cell antibody cloning technologies have enabled the molecular characterization of monoclonal antibodies against Plasmodium falciparum parasites, which has significantly enhanced our understanding of how these antibodies are generated, as well as their epitope specificity and binding modes.

Universal cells — here defined as cells that are invisible to the immune system — could potentially have many uses in transplantation medicine. This Review discusses how far we have come in creating such cells and the lessons that nature can teach us about immune evasion.

Platelets are best known for their roles in haemostasis, but they also contribute to host immunity. In this Review, Gaertner and Massberg consider how platelets ‘patrol the vascular highway’ to shape immune responses during infection and cancer.

Emerging studies highlight cell metabolism as a crucial regulator of T cell quiescence and activation. This Review describes how immunological cues and nutrients fine-tune metabolic programmes and signalling networks that together promote T cell quiescence exit.

Here, the authors describe how metabolic disorders, such as type 2 diabetes and nonalcoholic fatty liver disease, are driven by alterations in the composition of the intestinal microbiota and its metabolites, which translocate from the gut across a disrupted intestinal barrier and contribute to metabolic inflammation.

The identification of suitable tumour-specific antigens, which can be targeted by vaccine-based or T cell-based immunotherapies, is challenging. This Review explores the potential of alternative splicing to generate unique tumour antigens and discusses methods for their identification.