Endothelial autophagy blockade fosters anti-cancer immunity.

The discovery of immune checkpoints, consisting of transmembrane ligand-receptor protein pairs that negatively regulate the CD8 T-cell-mediated immune response by antigen-presenting cells (APCs) and by cancer cells, has enabled a fundamental advancement of cancer therapies (Korman et al, 2022). Indeed, harnessing these homeostatic control mechanisms to their own advantage, tumor cells manage to defend themselves from the attack of the immune system, and immune checkpoint blockade (ICB) has proven to be an overwhelmingly successful antitumor therapeutic approach (Korman et al, 2022).

Vesicle choreographies keep up cell-to-extracellular matrix adhesion dynamics in polarized epithelial and endothelial cells.

In metazoans, cell adhesion to the extracellular matrix (ECM) drives the development, functioning, and repair of different tissues, organs, and systems. Disruption or dysregulation of cell-to-ECM adhesion promote the initiation and progression of several diseases, such as bleeding, immune disorders and cancer. Integrins are major ECM transmembrane receptors, whose function depends on both allosteric changes and exo-endocytic traffic, which carries them to and from the plasma membrane.

Neuropilin 1 and its inhibitory ligand mini-tryptophanyl-tRNA synthetase inversely regulate VE-cadherin turnover and vascular permeability.

The formation of a functional blood vessel network relies on the ability of endothelial cells (ECs) to dynamically rearrange their adhesive contacts in response to blood flow and guidance cues, such as vascular endothelial growth factor-A (VEGF-A) and class 3 semaphorins (SEMA3s). Neuropilin 1 (NRP1) is essential for blood vessel development, independently of its ligands VEGF-A and SEMA3, through poorly understood mechanisms. Grounding on unbiased proteomic analysis, we report here that NRP1 acts as an endocytic chaperone primarily for adhesion receptors on the surface of unstimulated ECs.