Prostaglandin E₂ impacts multiple stages of the natural killer cell antitumor immune response.

Tumor immune escape is a major factor contributing to cancer progression and unresponsiveness to cancer therapies. Tumors can produce prostaglandin E (PGE ), an inflammatory mediator that directly acts on Natural killer (NK) cells to inhibit antitumor immunity. However, precisely how PGE influences NK cell tumor-restraining functions remains unclear.

TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation.

TIGIT is an inhibitory receptor expressed on lymphocytes and can inhibit T cells by preventing CD226 co-stimulation through interactions in cis or through competition of shared ligands. Whether TIGIT directly delivers cell-intrinsic inhibitory signals in T cells remains unclear. Here we show, by analysing lymphocytes from matched human tumour and peripheral blood samples, that TIGIT and CD226 co-expression is rare on tumour-infiltrating lymphocytes.

Analyzing Single Cell Secretions by "Shadow Imaging".

Here, we describe a method, which we term "shadow imaging," to analyze the secretions of individual cells at immune synapses or other cell contacts. Following immune synapse formation and cellular activation on ligand-rich slides, the position of each cell is recorded using a pulsed immunofluorescence stain against the proteins on the ligand-rich slide surface. The pulsed stain does not penetrate the synaptic cleft, resulting in an unlabeled region or "shadow" beneath cells that is retained following cellular detachment.

STORM imaging reveals the spatial arrangement of transition zone components and IFT particles at the ciliary base in Tetrahymena.

The base of the cilium comprising the transition zone (TZ) and transition fibers (TF) acts as a selecting gate to regulate the intraflagellar transport (IFT)-dependent trafficking of proteins to and from cilia. Before entering the ciliary compartment, IFT complexes and transported cargoes accumulate at or near the base of the cilium. The spatial organization of IFT proteins at the cilia base is key for understanding cilia formation and function.

Synaptic secretion from human natural killer cells is diverse and includes supramolecular attack particles.

Natural killer (NK) cells form immune synapses to ascertain the state of health of cells they encounter. If a target cell triggers NK cell cytotoxicity, lytic granules containing proteins including perforin and granzyme B, are secreted into the synaptic cleft inducing target cell death. Secretion of these proteins also occurs from activated cytotoxic T lymphocytes (CTLs) where they have recently been reported to complex with thrombospondin-1 (TSP-1) in specialized structures termed supramolecular attack particles (SMAPs).

Genetic diversity affects the nanoscale membrane organization and signaling of natural killer cell receptors.

Genetic diversity in human natural killer (NK) cell receptors is linked to resistance and susceptibility to many diseases. Here, we tested the effect of this diversity on the nanoscale organization of killer cell immunoglobulin-like receptors (KIRs). Using superresolution microscopy, we found that inhibitory KIRs encoded by different genes and alleles were organized differently at the surface of primary human NK cells.

Apico-basal Polarity Determinants Encoded by Genes Affect Ciliary Shaft Protein Composition, IFT Movement Dynamics, and Cilia Length.

One of the most obvious manifestations of polarity in epithelia is the subdivision of the cell surface by cell junctions into apical and basolateral domains. genes are among key regulators of this form of polarity. Loss of function disrupts the apical cell junction belt and overexpression expands the apical membrane size.