News & Comment

The early 2000s saw the first trials of checkpoint inhibitors in humans. Here, Jedd Wolchok discusses the first clinical results.

Katalin Karikó describes the discovery that replacing uridine with pseudouridine renders RNA non-immunogenic. This paved the way for developing mRNA for protein replacement therapy and, surprisingly, also for mRNA-based vaccine development.

Erika Pearce reflects on some of the early studies that helped to ignite the field of immunometabolism.

In this Journal Club, Zitvogel and Kroemer discuss a landmark study that initiated the genetic and molecular characterization of the immune–microbiota crosstalk.

Although it was known for decades that type I interferons are crucial for antiviral immunity, it was not until the discovery of cGAS and cGAMP signalling in 2013 that we understood how cytosolic DNA induces them in infected cells, as explained by Andrea Ablasser.

Derek Gilroy describes two studies that revealed an unexpected mechanism by which the resolution of inflammation can be induced.

Laura Mackay highlights seminal studies that shed light on tissue immunity and the unique biology of tissue-resident memory T cells.

Eric Vivier describes the unexpected discovery of new populations of innate-like lymphocytes and the development of the innate lymphoid cell nomenclature.

Feng Shao highlights the studies that led to the discovery and definition of pyroptosis as gasdermin-mediated programmed necrotic cell death.

Max Cooper recalls the discovery of variable lymphocyte receptors in lampreys and hagfish and explains the significance of this for understanding how adaptive immunity evolved in vertebrates.

Arturo Zychlinsky and Volker Brinkman recall the discovery of neutrophil extracellular traps.

David Schneider explains the concept of disease tolerance and describes the first observations of this phenomenon in animal models.

Eicke Latz recalls the discovery of the inflammasome in 2002 and how it revolutionized our understanding of inflammation and is now a target of new immunotherapeutics for inflammatory disease.

Shohei Hori recalls the early work that led to the identification of FOXP3 as the master regulator of regulatory T cells.

Mihai Netea tells us how the dichotomy of innate and adaptive immunity was blurred with the description of trained immunity in 2012 — a process by which innate immune cells and their progenitors store memory of past infections by epigenetic reprogramming.

Martin Guilliams and Charlotte Scott summarize some of the key studies that led to a refined dendritic cell nomenclature system based on ontogeny.

Gwendalyn Randolph reminds us of how our view of macrophage origin and identity has drastically changed over the past 15 years.

Beth Stevens and Matthew Johnson discuss the unexpected finding that classical complement components guide synaptic pruning in the brain and are necessary for healthy brain function.

A recent preprint describes a role for sensing of extracellular ATP through P2RX7 in the formation of memory T cells.

A recent preprint looking at the fate of exhausted human T cells after resolution of chronic HCV infection shows that they cannot completely recover and retain ‘traces’ of exhaustion markers.