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Certain cells bind so tightly to each other that, on occasion, one cell ends up inside another, usually with fatal consequences for the ingested cell. This involuntary cell death might help protect us from cancer.

Tissue-resident macrophages (TRM) are important mediators of local immunity. Here the authors show that the deficiency or inhibition of a kinase, WNK1, unlinks macrophage colony-stimulating factor signaling and resulted macropinocytosis with the downstream, potentially IRF8-mediated genetic program to bias progenitor differentiation to neutrophil instead of TRM.

An epithelial cell can be engulfed by its neighbour through entosis, which frequently results in the death of the entosed cell. Overholtzer and colleagues show that the autophagy machinery is recruited to single-membrane entotic vacuoles and promotes their fusion with lysosomes. Single-membrane macrophage phagosomes containing apoptotic cells are also targeted for destruction by the autophagy pathway.

For more than a century, scientists have observed cells internalized inside other cells. These cell-in-cell structures often consist of viable rather than apoptotic cells, and can form by the invasion of one cell into another, rather than by engulfment. This review will address how cell-in-cell structures might form and what physiological roles they might have.

This Opinion describes cell-in-cell processes in cancer, providing insight into their functional purpose in tumour tissue. Entosis is a unique process in which cancer cells are actively invaded by other cells, conferring them a competitive advantage that may drive cancer evolution.

Davidson et al. visualize ferroptosis-like cell death using three-colour live imaging in vivo and demonstrate its role in triggering macrophage recruitment but delaying resolution of inflammation during wounding in the Drosophila embryo.

Starved cancer cells and xenograft tumours in mice treated with ultrasmall silica nanoparticles undergo ferroptosis — a form of programmed cell death.

Chemotherapy-treated cancer cells that enter a non-dividing state called senescence can nevertheless boost cancer growth. The finding that these cells eat neighbouring cells reveals a mechanism that enables senescent cells to persist.

One of the major obstacles in nanoparticle-based therapy is to achieve tumour targeting, limiting non-specific accumulation of the nanoparticles. Here the authors propose the conjugation of anti-HER2 scFv fragments to the silica nanoparticles, increasing specificity and limiting the final size of the immunoconjugates below the renal clearance threshold.

Two complementary studies from the laboratories of Riegman et al. and Katikaneni et al., respectively, identify a key role for controlled wave-like propagation of lipid peroxide signalling during wound detection in vivo and in ferroptotic cell death.

Iacobuzio-Donahue and colleagues use integrated transcriptomic, histologic and mutational data to analyze squamous features of pancreatic ductal adenocarcinoma (PDAC), further refining the understanding of heterogeneity and evolution in PDAC.

A biochemical approach is used to understand how the ULK1 complex integrates signals from ATG proteins during autophagy. The interaction between ULK1-associated protein FIP200 and ATG16L1 of the ATG5 complex is revealed. This interaction is important for autophagy induced by amino acid starvation but not by glucose deprivation.

Hawk et al. show that RIPK1 activation during extracellular matrix detachment induces mitophagy through mitochondrial phosphatase PGAM5 to increase reactive oxygen species and non-apoptotic cell death, and that antagonizing RIPK1/PGAM5 enhances tumour formation.

Stat3 has been shown to regulate lysosome membrane permeabilization and cell death in vivo during post-lactation mammary gland involution. It is now revealed that Stat3 induces lysosome membrane permeabilization by causing phagocytosis of milk fat globules, which destabilize the lysosome membrane leading to leakage of cathepsin proteases.

Two complementary studies from the laboratories of Riegman et al. and Katikaneni et al., respectively, identify a key role for controlled wave-like propagation of lipid peroxide signalling during wound detection in vivo, and in ferroptotic cell death.

The Hippo pathway regulates proliferation and survival in Drosophila and mammals, although shared transcriptional targets of their effectors have not been identified. Mammalian YAP controls expression of the EGFR ligand amphiregulin to regulate epithelial-to-mesenchymal transition in mammary epithelial cells, and the EGFR pathway genetically interacts with Yorkie in Drosophila.

Aneploidy is frequently observed in cancer. It is now shown that aneploidy can arise by entosis, the process of live cell internalisation by a neighbouring cell. The internalised cell can interfere with host cell division and disrupt the formation of the contractile actin ring resulting in cytokinesis defects and aneuploidy.

To kill target cells, cytotoxic T lymphocytes (CTLs) form an immune synapse (IS) to elicit cell death and the IS then dissolves to allow for CTL serial killing. Huse et al. find that IS dissolution occurs concomitantly with cytoskeletal contraction of apoptotic targets and this is both necessary and sufficient for CTL dissociation

Cell-in-cell structures resulting from live cell engulfment were identified more than 100 years ago, but their physiological significance has remained largely obscure. Now Ni et al. identify a new role for cell-in-cell structure formation, called “in-cell infection” that spreads Epstein-Barr virus from infected B cells to epithelial cells, an activity that may predispose to cancer.

Mechanical deformability is known to increase during cancer progression. Now Ma et al. identify a therapeutic strategy that targets deformable cells by microparticle-based drug delivery.

The autophagy-related process LC3-Associated Phagocytosis, or LAP, is known to control the degradation of engulfed cells and microorganisms. Now Martinez et al. discover that LAP controls immune responses to dying cells and its inhibition leads to development of Systemic Lupus Erythematosus-like disease.