Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders

Abstract

Protein phosphatases act as key regulators of multiple important cellular processes and are attractive therapeutic targets for various diseases. Although extensive effort has been dedicated to phosphatase-targeted drug discovery, early expeditions for competitive phosphatase inhibitors were plagued by druggability issues, leading to the stigmatization of phosphatases as difficult targets. Despite challenges, persistent efforts have led to the identification of several drug-like, non-competitive modulators of some of these enzymes — including SH2 domain-containing protein tyrosine phosphatase 2, protein tyrosine phosphatase 1B, vascular endothelial protein tyrosine phosphatase and protein phosphatase 1 — reigniting interest in therapeutic targeting of phosphatases. Here, we discuss recent progress in phosphatase drug discovery, with emphasis on the development of selective modulators that exhibit biological activity. The roles and regulation of protein phosphatases in immune cells and their potential as powerful targets for immuno-oncology and autoimmunity indications are assessed.

Identification of a Novel Hypoxia-induced Inflammatory Cell Death Pathway

“…PTP1B also has direct effects in myeloid cells 62 and lymphocytes 63,64 ; whether the PTP1B/RNF213/CYLD/SPATA2 pathway is active in these cells remains unclear. PTP1B/TCPTP inhibitors are in clinical trials as anti-neoplastic agents 30 (NCT04777994), mainly because of its predicted immunostimulatory effects 63,65 . Our results suggest that PTP1B inhibition might also have important, salutary direct effects on tumors cell.…”

Visual monitoring of biocatalytic processes using small molecular fluorescent probes: strategies-mechanisms-applications

“…This biocatalytic process relies on phosphatases. [97][98][99] Therefore, the visual detection of phosphate hydrolysis is significant for a full understanding of the mechanism of biocatalysts and improved treatment strategies.…”

Inhibition of PTPN3 Expressed in Activated Lymphocytes Enhances the Antitumor Effects of Anti-PD-1 Therapy in Head and Neck Cancer, Especially in Hypoxic Environments

“…Protein phosphatases have attracted increasing attention as targets in cancer immunotherapy. 20 In eukaryotes, protein phosphatases reverse the phosphorylation of proteins using protein kinases and are crucial regulators of intracellular processes related to the maintenance of cellular homeostasis. 21 We focused on protein tyrosine phosphatase nonreceptor type (PTPN) 3, a member of the protein tyrosine phosphatase family that has been reported to negatively regulate T cell receptor (TCR) signaling in T cells by dephosphorylating tyrosine residues.…”

“…Protein phosphatases have attracted increasing attention as targets in cancer immunotherapy 20 . In eukaryotes, protein phosphatases reverse the phosphorylation of proteins using protein kinases and are crucial regulators of intracellular processes related to the maintenance of cellular homeostasis 21 .…”