Reviews & Analysis

Capturing cell organization in the tumor microenvironment using spatial proteomics can provide insight into the disease. A pair of studies applying this to advanced lung and brain tumors identifies organizational immune hallmarks that are associated with patient outcomes.

Antibody dynamics resulting from sequential immunization are complex, limiting the study of concepts such as ‘original antigenic sin’. Here, molecular fate-mapping defines an ‘addiction’ of boosted antibodies to primary clones, and OAS-like suppression of new clones, to a degree inversely related to boosting antigenic distance.

Taking advantage of intersectional genetics, Valente et al. report a novel strategy for tracking plasmacytoid dendritic cells (DCs) that enables their discrimination from conventional DCs and plasmacytoid DC–like cells, as well as transitional DCs.

Hidalgo and colleagues discuss general functional features of the neutrophil compartment that may be relevant in physiological scenarios such as specialization in naïve tissues, diversification and functional bias in inflammatory sites.

The NLRP10 protein is found to form an inflammasome complex in response to mitochondrial damage. Loss of NLRP10 from colonic epithelia promotes inflammatory bowel disease in a mouse model, while a variant predisposing to atopic dermatitis also shows loss of function.

Several panels of naturally arising antibodies against specific chemokines are closely correlated with various favorable COVID-19 outcomes, raising an opportunity to target the chemokine system for long COVID treatment.

Dendritic-cell-biased thymic seeding progenitors provide stromal support for early T cell development through the expression of membrane-bound TNF.

Homozygous expression of MHC-II alleles that confer susceptibility to type 1 diabetes limits the efficiency of thymic negative selection and allows for CXCR6⁺ pathogenic clones to orchestrate the disease process. Expression of a second MHC-II allele decreases β-islet CD4⁺ T cell affinity, and limits CD8 cross-priming and diabetes risk without presenting the cognate MHC-II islet self-antigen.

A new study by Zhou et al. identifies a unique microglia state in Nasu-Hakola disease and new potential therapeutic targets.

A serendipitous behavioral observation in a mouse line led to the discovery that macrophages modulate acute pain. The macrophage-derived protein SNX25 sets the threshold for acute pain through tonic NGF signaling to cutaneous sensory neurons.

The cholesterol metabolite receptor GPR183 regulates the secretion of IgA by intestinal plasma cells. This process requires epithelial cell sensing of commensal bacteria and the uptake of dietary cholesterol to generate the GPR183 ligand 7α,25-hydroxycholesterol. Upon GPR183 activation, IgA⁺ plasma cells remain at the center of intestinal villi and reduce their antibody secretion.

Research shows that Vδ1 and Vδ3 γδ T cells that express PD-1 and display potent cytotoxic functions are key immune responders in HLA-class-I-negative colon cancers subjected to immune checkpoint blockade therapy.

Prinz and colleagues discuss myeloid cell heterogeneity in the CNS and how cells are recruited and migrate into CNS niches.

Intrathymic dendritic cell (DC)-biased precursors act as hematopoietic stromal cells that support the generation of human T cell progenitors from hematopoietic progenitor cells, via crosstalk with immature thymocytes that express TNF receptor 2. This function of DC precursors can be exploited to generate T cell precursors and competent T cells for cell therapy.

In addition to the acute phase of SARS-CoV-2 infection, a significant percentage of patients experience a prolonged illness with varying symptomatology. Longitudinal SARS-CoV-2 patient-centric immunologic, inflammatory and metabolic data collection has allowed the generation of a composite signature to predict recovery.

Schwartz et al. propose that the antiviral type I interferon response in the brain’s choroid plexus might lead to cognitive sequelae in COVID-19.

T_H17 cells combat infection but can also drive pathological inflammation. A T_H17 cell NLRP3–caspase-8–caspase-3–GSDME axis is now shown to release the alarmin IL-1α without triggering cell death.

Human resident memory T (T_RM) cells clonally segregate in distinct tissues, with gene expression signatures tailored to those sites. Hence, beyond a shared language of residency, T_RM cells may acquire local dialects to provide site-specific immunity.

Exhausted effector T cells accumulate in tumors and are the intended targets of cancer immunotherapy. New data suggest that upon infiltration and subsequent exhaustion in the tumor microenvironment, these T cells can take on an immunosuppressive function — and work against the immune response to cancer.

Starting on 19 September 2022, the very first ImmunOctoberfest conference took place in Raitenhaslach, Germany, bringing together scientists from all over the world to discuss ‘bridging innovation and translation in T cell immunotherapy’.