The human G protein-coupled ATP receptor P2Y is a target for anti-inflammatory strategies.

Background And Purpose: The ATP receptor P2Y , which couples to G and G proteins, senses cell stress and promotes cytoprotective responses. P2Y receptors are upregulated during differentiation of M2 macrophages. However, it is unclear whether and how P2Y receptors contribute to the anti-inflammatory properties of M2 macrophages.

The Human G Protein-Coupled ATP Receptor P2Y Is Associated With IL-10 Driven Macrophage Differentiation.

The G protein-coupled P2Y receptor is known to sense extracellular ATP during inflammatory and immune responses. The dinucleotide NAD has also been proposed to be a P2Y receptor ligand but its role is less clear. Here, we have examined for the first time human P2Y receptor protein levels and show that the receptor was upregulated during polarization of M2 macrophages.

Rare, but Severe: Vasculitis and Checkpoint Inhibitors.

In the last years, immunotherapy has become a mainstay of cancer treatment. Owing to its increasing application in clinical practice, novel and rare, but severe, immune-related adverse events such as vasculitis are now being described more frequently. Vasculitis occurs as part of a primary immune disorder but might be induced additionally by substances such as checkpoint inhibitors, which boost the immune system, and thus can also appear as an immune-related adverse event.

Mevalonate Metabolism in Cancer Stemness and Trained Immunity.

Mevalonate metabolism provides cancer and immune cells with diverse products to ensure cell functionality. Similar metabolic reprogramming that raises mevalonate metabolism to higher levels appears to drive both, epithelial mesenchymal transition (EMT) of cancer cells, a reverse differentiation program that generates cancer cells with stem cell properties, and immune cell training for increased responsiveness to secondary stimulation. In this review, we address how mevalonate metabolism supports cancer development and stemness on the one hand, and on the other promotes immune responsiveness.

Mevalonate Metabolism in Immuno-Oncology.

Immuno-oncology not only refers to the multifaceted relationship between our immune system and a developing cancer but also includes therapeutic approaches that harness the body's immune system to fight cancer. The recognition that metabolic reprogramming governs immunity was a key finding with important implications for immuno-oncology. In this review, we want to explore how activation and differentiation-induced metabolic reprogramming affects the mevalonate pathway for cholesterol biosynthesis in immune and cancer cells.