Reviews & Analysis

The immune response to dengue virus infection is a well-coordinated balancing act. New research shows that an imbalanced response — driven partially by the productive infection of antigen-presenting cells — is associated with progression to severe disease.

Bantug and Hess discuss the metabolic interplay between tumor-resident cells and how the effect of metabolism-targeted anticancer strategies on non-transformed or immune cells in the tumor needs to be considered.

Here the authors review CAR T cell engineering and immunotherapy for cancer and juxtapose state-of-the-art developments with CAR NK cells as part of our Cancer Immunology series of Reviews.

We are in the midst of an explosion of multiomics and spatial data along with constant innovation of the tools used to study these data. In this Review article, as part of our Cancer Immunology and Immunotherapy series, the authors discuss these innovations and their application to study the tumor microenvironment.

Interleukin-27 (IL-27) is a pleiotropic cytokine known for its diverse immune regulatory properties. Although innate immune cells are considered the major cellular sources of IL-27, we found that gut regulatory T cells (T_reg cells) secrete IL-27 under inflammatory conditions, allowing them to selectively limit intestinal helper T17 cell (T_H17 cell) responses in various disease settings.

Cancer cells often overexpress CD47, which triggers the macrophage receptor SIRPα to elude anti-tumor immunity. We found that CD47 also suppresses phagocytosis by masking a pro-phagocytic ligand, SLAMF7, on tumor cells. We generated a first-in-class SLAMF7 antibody, which dissociated the CD47–SLAMF7 cis interaction, enabling anti-tumor immunity during SIRPα blockade.

After acute injury to skeletal muscle, an ‘early responder’ subtype of stromal cells rapidly produces an array of inflammatory mediators. Disruption of this response causes abnormal accumulation of several adaptive lymphocyte populations, a prolongation of inflammation, and an effect on tissue regeneration.

Regulatory T (T_reg) cells maintain the balance between immune protection and pathology. Research has now found that intestinal T_reg cells produce IL-27 to restrain T_H17 cell-mediated immune responses, effectively restricting autoimmune inflammation and limiting T cell responses to certain gut pathogens.

Determining the immune crosstalk between macrophages and NK cells in bronchioalveolar lavage fluid during SARS-CoV-2 infection in macaques identifies immunoregulatory properties of NK cells and their implications for viral persistence.

S100A8 and S100A9 are cytosolic alarmins with autocrine functions that facilitate neutrophil recruitment. Rapid, transient gasdermin-D pore formation is now shown to mediate secretion of these proteins in response to E-selectin without driving pyroptosis.

Two new studies in which apoE expression in mice is manipulated provide insights into the roles of microglial apoE in neurodegeneration.

Severe COVID-19 is marked by excessive inflammation that can persist after infection. The commensal yeast Candida albicans is now implicated in the acute and chronic immunopathology of COVID-19.

Hogan et al. identify a co-immunodominant influenza peptide presented in mice by MHC-E, a nonclassical class I molecule. Notably, the peptide derives from a 16-residue alternative reading frame translated by leaky ribosome scanning of the M1 mRNA and is recognized by conventional CD8⁺ T cells.

A trimodal single-cell assay reveals a previously unknown T cell subset and cellular state differences between children and older adults that might contribute to age-specific immunity.

Immune checkpoint inhibitors provide beneficial anti-tumor immunity but risk immune-related adverse events occurring in normal tissues. Notably, selective deletion of PGLYRP1, a protein expressed by several immune cells, protects against tumor cell growth and autoimmunity.

Genetic and environmental diversity are major drivers of macrophage transcriptional responses, but the mechanisms that underlie the relative contributions of gene-by-environment interactions to transcriptional responses of tissue macrophages are unclear. We defined the relative effect of cis regulation, cell-autonomous trans regulation, and non-cell-autonomous trans regulation of Kupffer cell gene expression.

Santosa and Sun draw parallels from T cell biology to explore the key features of immune memory in innate lymphocytes.

For decades, beta-blockers have been used widely to treat cardiovascular diseases. Surprisingly, new data show how these inhibitors can also improve immunotherapy against tumors and chronic infections.

Kupffer cells, hepatic resident macrophages, are the first line of defense against liver metastases by engulfing disseminated malignant cells. We found that ERMAP expressed on tumor cells binds to galectin-9 and dectin-2 on Kupffer cells to deliver pro-phagocytosis ‘eat me’ signals to Kupffer cells to restrict liver metastases.

The first conference on ‘Infection and Immunity’ was organized by the Institute for Basic Science and Korean Association of Immunologists and held in Daejeon, South Korea, from 12 to 14 July 2023. The conference focused on the biology of CD8⁺ T cells in the context of viral disease and cancer.