Wnt/beta-catenin pathway: modulating anticancer immune response

Sachin Gopalkrishna Pai; Benedito A Carneiro; Jose Mauricio Mota; Ricardo Costa; Caio Abner Leite; Romualdo Barroso-Sousa; Jason Benjamin Kaplan; Young Kwang Chae; Francis Joseph Giles

doi:10.1186/s13045-017-0471-6

Wnt/beta-catenin pathway: modulating anticancer immune response

J Hematol Oncol. 2017 May 5;10(1):101. doi: 10.1186/s13045-017-0471-6.

Authors

Sachin Gopalkrishna Pai^{1

2

3}, Benedito A Carneiro^{4

5}, Jose Mauricio Mota⁶, Ricardo Costa^{4

5}, Caio Abner Leite⁷, Romualdo Barroso-Sousa⁸, Jason Benjamin Kaplan^{4

5}, Young Kwang Chae^{4

5}, Francis Joseph Giles^{4

5}

Affiliations

¹ Developmental Therapeutics Program, Division of Hematology/Oncology, Feinberg School of Medicine, Chicago, IL, USA. [email protected].
² Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA. [email protected].
³ Current Address: Department of Interdisciplinary Clinical Oncology, Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL, USA. [email protected].
⁴ Developmental Therapeutics Program, Division of Hematology/Oncology, Feinberg School of Medicine, Chicago, IL, USA.
⁵ Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
⁶ Instituto do Câncer do Estado de São Paulo, University of São Paulo, São Paulo, Brazil.
⁷ A.C. Camargo Cancer Center, São Paulo, Brazil.
⁸ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Abstract

Wnt/β-catenin signaling, a highly conserved pathway through evolution, regulates key cellular functions including proliferation, differentiation, migration, genetic stability, apoptosis, and stem cell renewal. The Wnt pathway mediates biological processes by a canonical or noncanonical pathway, depending on the involvement of β-catenin in signal transduction. β-catenin is a core component of the cadherin protein complex, whose stabilization is essential for the activation of Wnt/β-catenin signaling. As multiple aberrations in this pathway occur in numerous cancers, WNT-directed therapy represents an area of significant developmental therapeutics focus. The recently described role of Wnt/β-catenin pathway in regulating immune cell infiltration of the tumor microenvironment renewed the interest, given its potential impact on responses to immunotherapy treatments. This article summarizes the role of Wnt/β-catenin pathway in cancer and ongoing therapeutic strategies involving this pathway.

Keywords: Cancer immune regulation; Immune exclusion; Immunotherapy; Wnt; β-catenin.

Publication types

Review

MeSH terms

Acyltransferases / antagonists & inhibitors
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Cell Communication / drug effects
Clinical Trials as Topic
Humans
Immunotherapy*
Immunotherapy, Adoptive
Macrophages / drug effects
Membrane Proteins / antagonists & inhibitors
Molecular Targeted Therapy*
Neoplasm Proteins / antagonists & inhibitors*
Neoplasm Proteins / physiology
Neoplasms / drug therapy*
Neoplasms / immunology
Observational Studies as Topic
T-Lymphocyte Subsets / immunology
Tankyrases / antagonists & inhibitors
Tumor Escape / drug effects
Tumor Escape / immunology
Tumor Microenvironment
Wnt Proteins / antagonists & inhibitors*
Wnt Proteins / physiology
Wnt Signaling Pathway / drug effects*
Wnt-5a Protein / agonists
beta Catenin / antagonists & inhibitors*
beta Catenin / physiology

Substances

Antineoplastic Agents
CTNNB1 protein, human
Membrane Proteins
Neoplasm Proteins
WNT5A protein, human
Wnt Proteins
Wnt-5a Protein
beta Catenin
Acyltransferases
PORCN protein, human
Tankyrases
TNKS protein, human