Modulation of Inflammatory Responses by Wnt/β-Catenin Signaling in Dendritic Cells: A Novel Immunotherapy Target for Autoimmunity and Cancer.
The Wnt/β-catenin pathway is an evolutionarily conserved signaling pathway critical for several biological processes. An aberrant Wnt/β-catenin signaling is linked to several human diseases. Emerging studies have highlighted the regulatory role of the Wnt/β-catenin signaling pathway in normal physiological processes of parenchymal and hematopoietic cells. Recent studies have shown that the activation of Wnt/β-catenin pathway in dendritic cells (DCs) play a critical role in mucosal tolerance and suppression of chronic autoimmune pathologies. Alternatively, tumors activate Wnt/β-catenin pathway in DCs to induce immune tolerance and thereby evade antitumor immunity through suppression of effector T cell responses and promotion of regulatory T cell responses. Here, we review our work and current understanding of how Wnt/β-catenin signaling in DCs shapes the immune response in cancer and autoimmunity and discuss how Wnt/β-catenin pathway can be targeted for successful therapeutic interventions in various human diseases.
Cancer Immunology, Inflammation, and Tolerance Program, Georgia Cancer Center, Augusta University , Augusta, GA , USA.
Amol
A
Suryawanshi
Janssen Research & Development , Spring House, PA , USA.
Raghu K
RK
Tadagavadi
Cancer Immunology, Inflammation, and Tolerance Program, Georgia Cancer Center, Augusta University , Augusta, GA , USA.
Daniel
D
Swafford
Cancer Immunology, Inflammation, and Tolerance Program, Georgia Cancer Center, Augusta University , Augusta, GA , USA.
Santhakumar
S
Manicassamy
Immune-tolerance; Immuno-oncology; Wnt; antitumor immunity; autoimmune diseases; dendritic cells; immunotherapy; β-catenin