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Combined immunotherapy using checkpoint blockade (anti-CTLA4 and anti-PD-1) and the DPP4 inhibitor sitagliptin reveals the existence of a T cell– and eosinophil-targeted immunotherapy approach for solid tumors.
Exhausted cytotoxic T lymphocytes (CTLs) express the receptor PD-1 as a key signature. Haining and colleagues show that there are different ‘depths’ of exhaustion with a subset of exhausted CTLs that retain polyfunctionality and are responsive to PD-1 blockade.
It remains difficult to distinguish cognate APC–T cell interactions in human tissue sections. Clark and colleagues have developed an imaging–machine-learning pipeline that uses deep convolutional and tuned neural networks to identify the combination of distance and cell-shape features that can discriminate between bystander human APC–T cell interactions and cognate interactions in situ.
Stemness is crucial for the maintenance of long-term T cell memory. Gattinoni and colleagues demonstrate that the transcription factor c-Myb is essential for the establishment of a stemness program in the CD8+ T cell memory compartment.
Cross-protective responses across all strains of influenza virus (IAV, IBV and ICV) are a key goal of universal vaccines against influenza. Kedzierska and colleagues identify cytotoxic T cells present in blood and lungs of healthy people that are directed against all strains of influenza virus.
An intricately linked homeostasis exists between the gut microbiome and host immune system. Scheffold and colleagues show that intestinal Treg cells upregulate the transcription factor c-Maf in response to specific signals from the gut microenvironment to establish host–microbiota homeostasis.
Eosinophils have been described mainly in allergy settings but are increasingly appreciated as being involved in other aspects of immunity. Albert and colleagues use a clinically approved inhibitor of the dipeptidyl peptidase DPP4 to facilitate the recruitment of eosinophils to mouse tumors, where they are essential in tumor destruction.
The transition of the fetus from the womb to the external world represents an extraordinary challenge. The generation of memory T cells before birth may serve an important role in preparation for this fundamental transition.
A multivalent vaccine that presents diverse influenza virus subtype H1 hemagglutinins on its surface induces broadly neutralizing antibodies in an animal model by displaying conserved epitopes at higher density than strain-specific epitopes.
Dendritic cells (DCs) have been suggested to express a functional NLRP3 inflammasome. Gerlic and colleagues demonstrate, however, that bone marrow–derived DCs completely lack NLRP3 inflammasome activity and that the bulk of splenic DCs lack or have only minimal activity.
Antigenic variation of influenza A viruses necessitates the annual reformulation of vaccines. Kanekiyo et al. develop a mosaic nanoparticle vaccine against influenza virus that is able to elicit neutralizing antibodies that span nearly 100 years of variation of influenza A virus.
In patients with rheumatoid arthritis, decreased abundance of the N-myristoyltransferase NMT1 in CD4+ T cells prevents N-myristoylation of the AMP-activated protein kinase AMPK and its localization to the lysosomal membrane, which leads to increased activation of the metabolic checkpoint kinase complex mTORC1 and proinflammatory T cell phenotypes.
The zinc transporter ZIP7 positively regulates signaling via the BCR during early B cell development in mice and humans. Impairment of ZIP7 function results in a novel primary immunodeficiency.
Zinc is important for normal immunity but its mechanistic actions are poorly understood. Hambleton and colleagues identify defects in Zn2+ transport that underpin a novel human immunodeficiency characterized by loss of mature B cells.
Pathogenic human CD4+ T cells in rheumatoid arthritis have hyperactivated metabolism. Weyand and colleagues show that this phenotype is associated with less myristoylation of the energy sensor AMPK and dysregulated metabolic sensor mTORC1.