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Jan 27, 2024;24 (1): 15.

WNT/β-catenin regulatory roles on PD-(L)1 and immunotherapy responses.

Keywan Mortezaee
Author Information
  1. Keywan Mortezaee: Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran. keywan987@yahoo.com.
PMID: 38280119 DOI: 10.1007/s10238-023-01274-z

Abstract

Dysregulation of WNT/β-catenin is a hallmark of many cancer types and a key mediator of metastasis in solid tumors. Overactive β-catenin signaling hampers dendritic cell (DC) recruitment, promotes CD8 T cell exclusion and increases the population of regulatory T cells (Tregs). The activity of WNT/β-catenin also induces the expression of programmed death-ligand 1 (PD-L1) on tumor cells and promotes programmed death-1 (PD-1) upregulation. Increased activity of WNT/β-catenin signaling after anti-PD-1 therapy is indicative of a possible implication of this signaling in bypassing immune checkpoint inhibitor (ICI) therapy. This review is aimed at giving a comprehensive overview of the WNT/β-catenin regulatory roles on PD-1/PD-L1 axis in tumor immune ecosystem, discussing about key mechanistic events contributed to the WNT/β-catenin-mediated bypass of ICI therapy, and representing inhibitors of this signaling as promising combinatory regimen to go with anti-PD-(L)1 in cancer immunotherapy. Ideas presented in this review imply the synergistic efficacy of such combination therapy in rendering durable anti-tumor immunity.

Keywords

Immune checkpoint inhibitor (ICI) Programmed death-1 (PD-1) Programmed death-ligand 1 (PD-L1) Resistance Tumor microenvironment (TME) β-catenin

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MeSH Term

Humans
B7-H1 Antigen
beta Catenin
Immunotherapy
Neoplasms
Programmed Cell Death 1 Receptor
Tumor Microenvironment
Wnt Signaling Pathway

Chemicals

B7-H1 Antigen
beta Catenin
Programmed Cell Death 1 Receptor
CD274 protein, human
Journal Article Review

Word Cloud

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